WEBVTT 1 00:00:08.750 --> 00:00:11.500 Hello, I'm Heather Nelson, and I'm a clinical chemistry 2 00:00:11.500 --> 00:00:14.900 fellow at the University of Utah and Iope laboratories. 3 00:00:15.216 --> 00:00:18.666 Today I'm going to discuss with you diabetes diagnosis 4 00:00:19.100 --> 00:00:21.733 and management. 5 00:00:21.733 --> 00:00:24.466 The learning objectives for today are to be able to describe 6 00:00:24.466 --> 00:00:27.466 and differentiate type one and type two diabetes. 7 00:00:27.733 --> 00:00:30.950 Identify the criteria required for diagnosis of diabetes 8 00:00:31.150 --> 00:00:34.150 and the analytical methods we use in the clinical laboratory, 9 00:00:34.483 --> 00:00:38.233 as well as discuss blood glucose monitoring, insulin administration, 10 00:00:38.500 --> 00:00:41.500 and medications used in managing diabetes. 11 00:00:42.633 --> 00:00:45.650 let's talk about how our body gets energy. 12 00:00:46.366 --> 00:00:48.950 Carbohydrates are found in a wide 13 00:00:48.950 --> 00:00:51.950 array of both healthy and unhealthy foods. 14 00:00:52.033 --> 00:00:53.616 And when we consume these foods, 15 00:00:53.616 --> 00:00:56.900 carbohydrates are broken down to glucose during digestion. 16 00:00:57.400 --> 00:01:01.733 And that, glucose is then absorbed into the bloodstream. 17 00:01:02.233 --> 00:01:06.833 And it's carried to various organs in the body which use glucose for energy. 18 00:01:07.633 --> 00:01:10.183 And in order for the cells to utilize this glucose 19 00:01:10.183 --> 00:01:13.600 for energy, it must be taken up into the cells. 20 00:01:13.900 --> 00:01:17.383 And that helps maintain the blood glucose at constant levels. 21 00:01:17.983 --> 00:01:21.533 In the face of this dynamic glucose intake, as well as a dynamic 22 00:01:21.533 --> 00:01:22.633 energy expenditure. 23 00:01:25.066 --> 00:01:26.983 The pancreas represents a 24 00:01:26.983 --> 00:01:30.316 key player in maintaining blood glucose in a narrow range. 25 00:01:30.800 --> 00:01:33.233 The pancreas is located behind the stomach. 26 00:01:33.233 --> 00:01:37.033 In the upper left abdomen is a bi functional organ, 27 00:01:37.250 --> 00:01:41.533 with each compartment having distinct morphology and anatomical functions. 28 00:01:42.100 --> 00:01:46.000 The exocrine tissue accounts for about 98% of the 29 00:01:46.000 --> 00:01:49.516 total Mat mass, and it has a critical role in digestion. 30 00:01:50.183 --> 00:01:54.166 The acid or cells that make up the exocrine tissue secrete digestive 31 00:01:54.166 --> 00:01:58.783 enzymes into a branch ductal network that empty into the small intestine, 32 00:01:59.950 --> 00:02:02.750 scattered throughout the exocrine tissue, or small 33 00:02:02.750 --> 00:02:05.750 clusters of cells called islets of Langhorne. 34 00:02:05.783 --> 00:02:08.183 The islets are composed of endocrine cells 35 00:02:08.183 --> 00:02:11.183 that secrete hormones to regulate blood glucose. 36 00:02:11.200 --> 00:02:14.716 The beta cell is the most abundant 37 00:02:14.716 --> 00:02:17.750 cell within the islet, and it secretes insulin. 38 00:02:17.933 --> 00:02:22.666 Insulin stimulates glucose uptake, which in effect reduces blood glucose. 39 00:02:23.783 --> 00:02:25.366 The alpha cell is the 40 00:02:25.366 --> 00:02:28.933 second, most predominant cell type in the islet, 41 00:02:29.333 --> 00:02:32.983 and it secretes glucagon, which stimulates 42 00:02:32.983 --> 00:02:36.733 glycogen cis and gluconeogenesis, which helps, 43 00:02:36.983 --> 00:02:40.900 increase blood glucose in times of prolonged fasting. 44 00:02:42.700 --> 00:02:45.616 There are some other cell types in the islet, but for the sake of this 45 00:02:45.616 --> 00:02:49.450 presentation, we'll, mostly discuss the function of the beta cell. 46 00:02:49.850 --> 00:02:52.850 And some on the alpha cell. 47 00:02:53.600 --> 00:02:56.316 So how is glucose handled in the body? 48 00:02:56.316 --> 00:03:00.133 As I said, when the body, when you consume food, it's 49 00:03:00.133 --> 00:03:03.133 broken down into simple sugars, which then are absorbed 50 00:03:03.133 --> 00:03:06.166 into the bloodstream, represented by these purple circles 51 00:03:06.983 --> 00:03:09.766 in response to the increasing blood glucose. 52 00:03:09.766 --> 00:03:12.700 The islets within the pancreas, in particular the beta cells, 53 00:03:12.700 --> 00:03:14.783 will secrete insulin. 54 00:03:14.783 --> 00:03:19.133 The insulin will go into the bloodstream and then act on peripheral tissues, 55 00:03:19.583 --> 00:03:23.183 such as the liver and muscle to stimulate glucose uptake, 56 00:03:23.450 --> 00:03:26.266 thereby maintaining normal levels of blood glucose. 57 00:03:27.316 --> 00:03:29.716 If any of these, 58 00:03:29.716 --> 00:03:32.633 mechanisms in the pathway go wrong, 59 00:03:32.633 --> 00:03:35.783 it results in elevated level of blood glucose in the role 60 00:03:35.783 --> 00:03:39.100 in the blood, whether it's lack of insulin secretion 61 00:03:39.316 --> 00:03:42.316 or lack of insulin sensitivity in the periphery. 62 00:03:43.066 --> 00:03:46.066 That brings us to, diabetes mellitus. 63 00:03:46.433 --> 00:03:50.116 Diabetes is a group of metabolic disorders characterized 64 00:03:50.116 --> 00:03:53.116 by abnormally elevated blood glucose levels, 65 00:03:54.500 --> 00:03:57.350 high blood glucose levels, and type one diabetes 66 00:03:57.350 --> 00:04:02.933 occurs due to a lack of insulin, consequent of immune mediated destruction. 67 00:04:03.233 --> 00:04:07.450 Of these insulin secreting beta cells in the pancreatic pancreatic islets. 68 00:04:08.900 --> 00:04:11.633 High blood glucose in type two diabetes 69 00:04:11.633 --> 00:04:14.633 is due to an ineffective use of insulin. 70 00:04:14.650 --> 00:04:18.950 So although the body's still producing insulin, the cells in the body 71 00:04:18.950 --> 00:04:22.033 do not respond to insulin to mediate glucose uptake. 72 00:04:23.233 --> 00:04:25.966 Another type of diabetes that you may have heard of 73 00:04:25.966 --> 00:04:29.800 is gestational diabetes, and this is a transient condition 74 00:04:30.233 --> 00:04:35.000 in which blood sugar levels become elevated during pregnancy and affects 75 00:04:35.000 --> 00:04:38.533 actually up to about 10% of women who are pregnant each year. 76 00:04:39.400 --> 00:04:42.833 But it typically resolves, after giving birth. 77 00:04:43.883 --> 00:04:44.983 And just to note, the 78 00:04:44.983 --> 00:04:47.983 medical term for high blood glucose is hypoglycemia. 79 00:04:47.983 --> 00:04:51.500 So I'll use those, that terminology throughout the presentation. 80 00:04:52.733 --> 00:04:56.250 So I had mentioned previously there's type one and type two diabetes. 81 00:04:56.250 --> 00:04:57.233 So let's get a little bit 82 00:04:57.233 --> 00:05:02.033 more into the details on, how these two forms of diabetes compare. 83 00:05:02.033 --> 00:05:05.900 So type one diabetes was formerly called juvenile diabetes. 84 00:05:05.900 --> 00:05:08.733 But we really don't use this terminology anymore 85 00:05:08.733 --> 00:05:12.683 because we know it can affect, it can have an onset in adults, 86 00:05:13.050 --> 00:05:16.000 although it typically has onset in, 87 00:05:16.000 --> 00:05:19.533 children instead of calling it juvenile diabetes. 88 00:05:19.533 --> 00:05:23.150 The more appropriate term is insulin dependent diabetes mellitus. 89 00:05:23.150 --> 00:05:27.533 And that's because the loss of insulin, secretion in these patients 90 00:05:27.533 --> 00:05:29.033 requires them to be on insulin. 91 00:05:29.033 --> 00:05:30.750 The insulin therapy, lifelong. 92 00:05:32.300 --> 00:05:33.266 It results from an 93 00:05:33.266 --> 00:05:36.500 autoimmune destruction of the insulin secreting beta cells. 94 00:05:36.500 --> 00:05:37.700 So it cannot be prevented. 95 00:05:37.700 --> 00:05:42.716 There's no dietary changes or lifestyle changes that will prevent this disease. 96 00:05:42.716 --> 00:05:45.716 Once the beta cells are destroyed by the immune system. 97 00:05:46.550 --> 00:05:49.916 And again, it requires lifelong insulin therapy 98 00:05:50.283 --> 00:05:54.533 in type one only accounts for about 5 to 10% of all diabetes cases. 99 00:05:55.733 --> 00:06:00.116 Type two on the other hand, it tends to develop at an older age, 100 00:06:00.116 --> 00:06:05.600 but it's becoming increasingly common in adolescence, and it occurs due 101 00:06:05.600 --> 00:06:10.166 to insulin resistance and a progressive loss of insulin secretion over time. 102 00:06:11.483 --> 00:06:14.966 It can be prevented with lifestyle changes, which we'll discuss. 103 00:06:14.966 --> 00:06:17.966 Largely related to die in exercise. 104 00:06:18.383 --> 00:06:21.450 And, patients with these may also need, 105 00:06:21.550 --> 00:06:24.633 oral medications and occasionally insulin if they're having 106 00:06:24.633 --> 00:06:27.716 trouble controlling their blood glucose and type 107 00:06:27.716 --> 00:06:32.000 two diabetes is a more common form, accounting for about 90% of the cases. 108 00:06:34.083 --> 00:06:36.000 Back to how glucose is handled. 109 00:06:36.000 --> 00:06:39.716 And compare, type one to the normal glucose we walk through. 110 00:06:40.083 --> 00:06:43.583 You can see here that in type one diabetes, the pancreas just does 111 00:06:43.583 --> 00:06:48.833 not secrete insulin in response to the elevated blood glucose. 112 00:06:48.833 --> 00:06:51.683 And that's because there's no longer beta cells present. 113 00:06:51.683 --> 00:06:54.683 And therefore there's an increased level of glucose in the blood. 114 00:06:55.766 --> 00:06:59.250 In comparison, in type two diabetes, we still have those beta cells, 115 00:06:59.250 --> 00:07:03.200 secreting insulin in response to elevated blood glucose. 116 00:07:03.750 --> 00:07:08.583 But the cells in the periphery aren't responding well to the, insulin. 117 00:07:08.583 --> 00:07:12.500 So they're not effectively taking up blood, the glucose from the blood. 118 00:07:12.783 --> 00:07:15.866 And therefore you still have that same net effect, which is the increased 119 00:07:15.866 --> 00:07:18.866 level of glucose in the blood. 120 00:07:19.283 --> 00:07:21.333 Diabetes symptoms vary 121 00:07:21.333 --> 00:07:24.333 depending on how much your blood sugar is elevated. 122 00:07:24.500 --> 00:07:29.883 Some people, especially with those those with prediabetes or type two diabetes, 123 00:07:30.283 --> 00:07:34.983 may sometimes not experience all these symptoms or even recognize them at first. 124 00:07:35.350 --> 00:07:38.000 However, in type one diabetes, the symptoms tend to 125 00:07:38.000 --> 00:07:41.000 come on more quickly and be more severe. 126 00:07:41.100 --> 00:07:46.500 However, because the symptoms of diabetes are all related to the effects of high 127 00:07:46.500 --> 00:07:50.750 blood glucose, they are very similar for both type one and type two diabetes, 128 00:07:51.200 --> 00:07:54.933 and those symptoms include, fatigue and weakness. 129 00:07:55.283 --> 00:07:57.600 They'll complain of always being tired. 130 00:07:57.600 --> 00:08:01.166 And this is because the body does not receive enough energy from the 131 00:08:01.383 --> 00:08:03.083 from the food they're ingesting, because they 132 00:08:03.083 --> 00:08:05.400 their body is not handling that glucose properly, 133 00:08:07.083 --> 00:08:08.933 poorly area or increase. 134 00:08:08.933 --> 00:08:12.566 Urination is also common in this occurs because the kidneys 135 00:08:12.566 --> 00:08:15.833 are trying to remove that excess sugar from the blood, 136 00:08:16.383 --> 00:08:19.383 which results in a higher urine production. 137 00:08:20.033 --> 00:08:25.316 And very similarly, for that reason, they'll have constant thirst. 138 00:08:25.983 --> 00:08:29.150 And this is because they're losing so much water 139 00:08:29.150 --> 00:08:32.450 through that increased urination that it triggers that thirst response. 140 00:08:34.033 --> 00:08:36.233 Poly failure or increased 141 00:08:36.233 --> 00:08:39.233 appetite is also associated with diabetes. 142 00:08:39.500 --> 00:08:42.300 And again, this is because the glucose from the food 143 00:08:42.300 --> 00:08:45.750 that the individuals are consuming doesn't enter the cells. 144 00:08:46.350 --> 00:08:49.500 Whether it's due to insulin resistance or lack of insulin production. 145 00:08:49.500 --> 00:08:52.800 So their body's response is thinking they need more energy, 146 00:08:52.800 --> 00:08:55.800 it stimulates the hunger drive. 147 00:08:55.983 --> 00:08:58.016 They can also have, sudden weight 148 00:08:58.016 --> 00:09:01.016 loss or wounds that won't heal. 149 00:09:01.450 --> 00:09:04.766 And they could also 150 00:09:04.766 --> 00:09:08.666 have sudden changes in vision as the body pulls water away from, 151 00:09:08.666 --> 00:09:13.083 from the eye, an attempt to compensate for that loss of fluid in the urine, 152 00:09:13.716 --> 00:09:16.716 so that that results in trouble focusing. 153 00:09:16.766 --> 00:09:19.316 They may also have numbness or tingling in the feet. 154 00:09:19.316 --> 00:09:23.450 This is more of a symptom that happens over time due to chronic, 155 00:09:23.450 --> 00:09:27.000 elevated blood glucose that can damage the nerves in the periphery. 156 00:09:28.316 --> 00:09:29.933 And they may also experienced 157 00:09:29.933 --> 00:09:33.633 sexual problems or, vaginal infections. 158 00:09:34.083 --> 00:09:36.533 And that's related to the high sugar in the blood. 159 00:09:36.533 --> 00:09:40.416 It creates a fertile breeding ground for the, bacteria 160 00:09:40.416 --> 00:09:43.416 or yeast to overgrow. 161 00:09:44.000 --> 00:09:47.000 There are many complications of uncontrolled diabetes. 162 00:09:47.100 --> 00:09:50.516 And these can be broken down to acute and chronic complications. 163 00:09:51.016 --> 00:09:55.050 Acute complications include diabetic ketoacidosis. 164 00:09:55.383 --> 00:09:58.166 And this occurs when your, body produces high 165 00:09:58.166 --> 00:10:01.166 level of blood acids called ketones. 166 00:10:01.533 --> 00:10:04.766 And it develops when your body can't produce enough insulin. 167 00:10:05.183 --> 00:10:08.183 So when your cells don't get the insulin they need for energy, 168 00:10:08.433 --> 00:10:12.266 your body begins to burn fat for energy, which produces those ketones. 169 00:10:13.233 --> 00:10:16.683 This condition is characterized by elevated plasma glucose, 170 00:10:16.683 --> 00:10:20.366 elevated plasma ketones, as well as a low plasma pH. 171 00:10:21.100 --> 00:10:24.083 It has a rapid onset, and it's much more common in type 172 00:10:24.083 --> 00:10:27.083 one diabetes, because the incident that's present, 173 00:10:27.150 --> 00:10:30.900 present in type two diabetics is enough to inhibit ketogenic. 174 00:10:32.633 --> 00:10:35.450 Another key complication that's more common in type 175 00:10:35.450 --> 00:10:40.616 two diabetes is hyper a similar hypoglycemic state or horse. 176 00:10:41.583 --> 00:10:45.000 And this is characterized by severe hypoglycemia. 177 00:10:45.000 --> 00:10:47.216 So the blood glucose is often higher than that. 178 00:10:47.216 --> 00:10:50.450 You see, in, diabetic ketoacidosis. 179 00:10:50.966 --> 00:10:54.683 It's also characterized by extreme hydration, dehydration, 180 00:10:55.083 --> 00:10:58.083 hyper molar plasma, and altered consciousness. 181 00:10:58.533 --> 00:11:02.433 This condition is also often precipitated 182 00:11:02.433 --> 00:11:06.866 by severe illness or stress, and can have more of a progressive onset. 183 00:11:06.866 --> 00:11:09.866 So this can develop over days. 184 00:11:09.983 --> 00:11:11.583 Opposite of these two conditions 185 00:11:11.583 --> 00:11:15.233 is hypoglycemia, which is not often thought of with diabetes. 186 00:11:15.233 --> 00:11:17.250 And this is low blood glucose. 187 00:11:17.250 --> 00:11:19.950 It can occur due to over medication. 188 00:11:19.950 --> 00:11:24.083 For example in a type one diabetic, if they inject too much insulin, 189 00:11:24.733 --> 00:11:28.100 or for from extended periods of fasting. 190 00:11:28.650 --> 00:11:32.433 And this is because those alpha cells in type one diabetics don't respond 191 00:11:32.433 --> 00:11:37.166 appropriately to secrete glucagon and help increase blood glucose. 192 00:11:38.600 --> 00:11:39.083 The chronic 193 00:11:39.083 --> 00:11:42.233 complications can be broken down into microvascular 194 00:11:42.233 --> 00:11:46.700 or microvascular, depending on the, blood vessels. 195 00:11:46.700 --> 00:11:48.450 They impact. 196 00:11:48.450 --> 00:11:52.433 And it develops over time due to the deleterious systemic 197 00:11:52.433 --> 00:11:55.433 effects of hyperglycemia on the vasculature. 198 00:11:56.250 --> 00:12:00.683 In more detail, the microvascular complications of diabetes 199 00:12:01.133 --> 00:12:03.683 are those long term complications 200 00:12:03.683 --> 00:12:06.683 that affect small, blood vessels. 201 00:12:06.800 --> 00:12:10.733 And these typically include diabetic retinopathy, 202 00:12:11.216 --> 00:12:14.033 nephropathy in neuropathy. 203 00:12:14.033 --> 00:12:18.383 Diabetic retinopathy is associated with progressive retinal damage 204 00:12:18.600 --> 00:12:22.916 that occurs in patients with long term diabetes and left untreated, 205 00:12:23.133 --> 00:12:26.666 this can lead to progressive loss of vision or even blindness. 206 00:12:28.016 --> 00:12:29.733 Diabetic nephropathy 207 00:12:29.733 --> 00:12:32.583 is caused by damage to the capillaries in the kidneys, 208 00:12:32.583 --> 00:12:36.566 which play a key role in filtration of the blood, and it's associated 209 00:12:36.566 --> 00:12:39.750 with a progressive decline in, renal function 210 00:12:40.050 --> 00:12:43.250 and can result and in stage, in stage renal disease. 211 00:12:43.616 --> 00:12:44.516 In fact, 212 00:12:44.516 --> 00:12:48.716 diabetic nephropathy is the leading cause of kidney failure in the United States. 213 00:12:49.983 --> 00:12:52.200 Diabetic neuropathy is 214 00:12:52.200 --> 00:12:55.583 nerve damage that most often occurs in the leg and feet. 215 00:12:56.150 --> 00:12:58.650 Symptoms may include pain, numbness, 216 00:12:58.650 --> 00:13:01.650 or tingling of the extremities. 217 00:13:01.683 --> 00:13:05.250 On the other side, we have microvascular, complications. 218 00:13:05.850 --> 00:13:10.550 Which are primarily diseases of the large blood vessels, such as the coronary 219 00:13:10.550 --> 00:13:14.583 arteries, the peripheral arteries, and the cerebral vasculature. 220 00:13:15.683 --> 00:13:18.266 Early, macro vascular disease 221 00:13:18.266 --> 00:13:21.933 is associated with atherosclerotic plaques in the vasculature, 222 00:13:22.200 --> 00:13:26.400 which supply blood to the heart, brain, limbs, and other organs. 223 00:13:27.300 --> 00:13:31.166 And late stages of macro vascular disease involve complete obstruction 224 00:13:31.166 --> 00:13:35.550 of these vessels, which can increase the risk of stroke, heart attack 225 00:13:36.033 --> 00:13:39.566 and pain, or death of the tissues in the extremities. 226 00:13:39.950 --> 00:13:42.950 Due to that lack of blood flow. 227 00:13:42.983 --> 00:13:44.850 Cardiovascular disease is a major 228 00:13:44.850 --> 00:13:48.750 cause of, morbidity and mortality in patients with diabetes, 229 00:13:48.750 --> 00:13:51.750 and that's related to these microvascular complications. 230 00:13:52.633 --> 00:13:57.516 And and that brings us to a discussion of the laboratory methods for diagnosis, 231 00:13:57.816 --> 00:14:01.816 which can all be found in the standards of medical care and diabetes. 232 00:14:02.116 --> 00:14:03.950 And I'll discuss each of the three. 233 00:14:03.950 --> 00:14:07.300 Components, starting with the hemoglobin A1, C 234 00:14:09.166 --> 00:14:10.450 hemoglobin is a 235 00:14:10.450 --> 00:14:14.300 protein molecule inside red blood cells that binds oxygen, 236 00:14:14.300 --> 00:14:17.750 allowing oxygen to be carried from the lungs to the rest of the body. 237 00:14:18.883 --> 00:14:21.333 Approximately 95% of adult 238 00:14:21.333 --> 00:14:25.066 hemoglobin is comprised of hemoglobin A in healthy individuals. 239 00:14:25.633 --> 00:14:28.633 Well, hemoglobin A to 240 00:14:29.050 --> 00:14:31.000 and very low levels of hemoglobin. 241 00:14:31.000 --> 00:14:35.000 Fetal hemoglobin make up a lesser extent of the remaining hemoglobin species. 242 00:14:36.400 --> 00:14:38.800 Hemoglobin A1 c makes up 243 00:14:38.800 --> 00:14:41.983 approximately 80% of the hemoglobin A1. 244 00:14:42.850 --> 00:14:45.966 So hemoglobin A1 C what is it exactly. 245 00:14:45.966 --> 00:14:49.216 It's the term used to report glycated hemoglobin. 246 00:14:49.600 --> 00:14:54.516 So some of the glucose clings to hemoglobin in a non enzymatic reaction. 247 00:14:55.366 --> 00:14:58.266 In everyone whether or not they have diabetes. 248 00:14:58.266 --> 00:14:59.050 And it stays there 249 00:14:59.050 --> 00:15:03.066 for the lifespan of the red blood cell which is about three months. 250 00:15:04.916 --> 00:15:05.833 Because of 251 00:15:05.833 --> 00:15:09.650 this, hemoglobin A1, C is widely used in the diagnosis 252 00:15:09.650 --> 00:15:12.650 as well as the monitoring of diabetic patients. 253 00:15:12.966 --> 00:15:16.550 The more glucose that is present in the bloodstream during the lifetime 254 00:15:16.550 --> 00:15:21.050 of the red blood cells, the higher the concentration of the hemoglobin A1, C 255 00:15:21.466 --> 00:15:25.633 and therefore it reflects average blue blood glucose over that period. 256 00:15:26.116 --> 00:15:29.916 So physicians can use the formula shown here 257 00:15:30.200 --> 00:15:33.200 to calculate an estimated average glucose 258 00:15:33.316 --> 00:15:36.316 based on the hemoglobin A1, c result. 259 00:15:36.466 --> 00:15:40.566 And the table to the right just shows what a hemoglobin A1 c would be. 260 00:15:40.566 --> 00:15:44.833 An estimated average glucose up to a a1 c of 12. 261 00:15:44.833 --> 00:15:49.066 And you can see the increasing a1 c is associated with an increasing 262 00:15:49.066 --> 00:15:52.066 estimated average glucose. 263 00:15:54.250 --> 00:15:57.516 Using hemoglobin A1 C has several advantages. 264 00:15:57.716 --> 00:16:01.366 Compared to some of the other tests we'll discuss, such as fasting plasma 265 00:16:01.366 --> 00:16:04.366 glucose and or glucose tolerance testing. 266 00:16:04.400 --> 00:16:06.700 First, it assesses glucose control 267 00:16:06.700 --> 00:16:10.483 over a three month window, so less frequent testing is needed. 268 00:16:11.150 --> 00:16:13.700 Additionally, it offers greater convenience 269 00:16:13.700 --> 00:16:16.816 as the patient is not required to fast before the test. 270 00:16:17.166 --> 00:16:21.016 And also it has a greater pre analytical stability compared to glucose, 271 00:16:21.016 --> 00:16:25.300 which can be metabolized by, red blood cells in the sample. 272 00:16:26.566 --> 00:16:28.266 It also has less day to day 273 00:16:28.266 --> 00:16:32.016 perturbations during different stress conditions, diet or illness. 274 00:16:32.750 --> 00:16:37.716 And can be very useful for monitoring long term glycemic control in patients 275 00:16:37.716 --> 00:16:40.716 rather than just getting an individual snapshot of one day. 276 00:16:41.650 --> 00:16:46.216 There are also some disadvantages of A1 c compared to blood glucose. 277 00:16:46.933 --> 00:16:51.016 It has a greater cost, lower sensitivity, 278 00:16:51.466 --> 00:16:54.466 at the designated cup point use clinically. 279 00:16:54.650 --> 00:16:58.600 And additionally it, it's an indirect measure. 280 00:16:58.600 --> 00:17:02.750 So there's an imperfect correlation between A1 c in average glucose. 281 00:17:03.200 --> 00:17:06.850 Particularly in certain individuals, the interpretation 282 00:17:06.850 --> 00:17:10.416 does depend on red blood cells having a normal life span. 283 00:17:10.633 --> 00:17:14.716 So any factor that may impact, hemoglobin glycation 284 00:17:14.716 --> 00:17:18.650 or the red blood cell lifespan, should be considered. 285 00:17:19.000 --> 00:17:22.750 Some of these factors include age, race or ethnicity. 286 00:17:23.150 --> 00:17:26.950 If they're on an HIV treatment, if they're anemic 287 00:17:26.950 --> 00:17:28.116 and certain hemoglobin not. 288 00:17:28.116 --> 00:17:30.166 But these can interfere with the measurement. 289 00:17:32.833 --> 00:17:35.500 There are many methods available to measure hemoglobin A1. 290 00:17:35.500 --> 00:17:40.250 See, the general concept underlying these methods is to separate 291 00:17:40.483 --> 00:17:45.000 glycated from non glycated hemoglobin and quantify the amount 292 00:17:45.016 --> 00:17:49.483 which most methods can be classified into one of two groups. 293 00:17:49.483 --> 00:17:51.700 According to the assay principle, 294 00:17:51.700 --> 00:17:56.233 the first group uses methods that measure hemoglobin A1 C on the basis 295 00:17:56.233 --> 00:18:00.066 of charge differences between glycated and non glycated components 296 00:18:00.650 --> 00:18:03.650 and these include cation exchange chromatography 297 00:18:04.033 --> 00:18:07.033 and capillary electrophoresis. 298 00:18:08.983 --> 00:18:13.866 Alternatively, there's methods that use structural differences 299 00:18:13.866 --> 00:18:16.866 to separated the separate the hemoglobin 300 00:18:17.016 --> 00:18:19.666 and this the most common is immunoassay. 301 00:18:19.666 --> 00:18:23.983 And then also affinity chromatography can be used. 302 00:18:25.000 --> 00:18:27.316 It should also be mentioned that hemoglobin 303 00:18:27.316 --> 00:18:30.650 A1 c point of care analyzers are available. 304 00:18:31.416 --> 00:18:34.416 Point of care testing devices which are located in 305 00:18:34.416 --> 00:18:37.750 physician offices and allow more rapid results. 306 00:18:38.900 --> 00:18:41.716 However, most of them are only approved 307 00:18:41.716 --> 00:18:46.933 for monitoring patients and should not be used for the diagnosis. 308 00:18:46.933 --> 00:18:51.316 There are few point of care devices FDA approved for diagnosis, 309 00:18:51.850 --> 00:18:55.033 but it must be used in the clinical setting for which they are clear. 310 00:18:56.916 --> 00:18:59.466 In the clinical lab, one of the more common methods 311 00:18:59.466 --> 00:19:02.466 for hemoglobin A1, C is to measure it by, 312 00:19:02.616 --> 00:19:05.716 high performance liquid chromatography or HPLC. 313 00:19:05.716 --> 00:19:09.733 C HPLC separates the hemoglobin A1 C 314 00:19:09.916 --> 00:19:13.483 from other hemoglobin based on different charges. 315 00:19:13.933 --> 00:19:17.416 Shown here is a basic set up of an HPLC system. 316 00:19:17.766 --> 00:19:20.466 You have buffers of varying ionic strengths, 317 00:19:20.466 --> 00:19:24.616 a sample injection, a cation exchange column, and a detector. 318 00:19:25.450 --> 00:19:28.550 If we take a zoomed in look at the column where we're actually 319 00:19:28.550 --> 00:19:32.166 separating the hemoglobin, we can see how the separation works. 320 00:19:32.600 --> 00:19:35.716 When blood is injected into a cation exchange cartridge, 321 00:19:36.200 --> 00:19:39.016 hemoglobin binds to the negatively charged surface 322 00:19:39.966 --> 00:19:40.366 and then 323 00:19:40.366 --> 00:19:44.266 buffer removes the less positively charged hemoglobin from the cartridge. 324 00:19:44.716 --> 00:19:47.800 And then, as the ionic strength of the buffer increases, 325 00:19:48.100 --> 00:19:51.100 the more positively charged fractions are displaced. 326 00:19:51.450 --> 00:19:54.850 Each hemoglobin is then read on a detector 327 00:19:54.850 --> 00:19:57.850 as it loots and is reported on a chromatogram, 328 00:19:58.000 --> 00:20:02.800 and the area under each of these hemoglobin curves is, quantified. 329 00:20:03.316 --> 00:20:06.816 And then you can calculate the ratio of the area 330 00:20:06.816 --> 00:20:10.816 under the curve for the a1 c to the total area of all curves. 331 00:20:10.816 --> 00:20:13.816 In order to get that percent hemoglobin A1 C. 332 00:20:15.400 --> 00:20:17.983 Another method sometimes used to measure 333 00:20:17.983 --> 00:20:21.850 hemoglobin A, c is capillary electrophoresis in. 334 00:20:21.850 --> 00:20:23.716 This method has a similar concept. 335 00:20:23.716 --> 00:20:27.666 However, molecules are separated by their electric mobility, 336 00:20:27.666 --> 00:20:30.666 so this is based on both charge and size. 337 00:20:31.100 --> 00:20:33.700 And they're separated in alkaline buffer. 338 00:20:33.700 --> 00:20:36.216 Of a specific pH. 339 00:20:36.216 --> 00:20:38.350 The sample is injected 340 00:20:38.350 --> 00:20:41.650 at the anodic end, and then a high voltage is applied. 341 00:20:42.016 --> 00:20:46.266 And through a combination of electromotive and electro osmotic forces, 342 00:20:46.633 --> 00:20:50.650 hemoglobin are separated and then detected at the, cathodic 343 00:20:50.650 --> 00:20:54.966 end of the capillary with a wavelength of 450 nanometers, 344 00:20:55.400 --> 00:20:59.266 which is the absorbance wavelength specific for hemoglobin. 345 00:21:00.650 --> 00:21:01.416 Similar to the 346 00:21:01.416 --> 00:21:06.800 HPLC method, a chromatogram is generated in which percent hemoglobin A1C 347 00:21:06.816 --> 00:21:09.966 can be calculated based on the area under the curve 348 00:21:11.266 --> 00:21:14.416 and the HPLC that I just discussed on the previous slide. 349 00:21:14.416 --> 00:21:18.566 As well as this capillary electrophoresis separate different hemoglobin 350 00:21:18.566 --> 00:21:20.116 S into different zones, 351 00:21:20.116 --> 00:21:23.450 so they are differentially affected by hemoglobin variants 352 00:21:23.450 --> 00:21:27.916 that could potentially interfere with the hemoglobin A1, c measurement. 353 00:21:28.600 --> 00:21:31.600 If they allu at the same time as the a1 c 354 00:21:31.700 --> 00:21:35.200 So shown here is actually a great resource that lists the effect 355 00:21:35.200 --> 00:21:39.883 of some of these hemoglobin variants on different, hemoglobin A1, 356 00:21:39.883 --> 00:21:43.566 C measurements and this, this resource can be used to help determine 357 00:21:43.566 --> 00:21:46.700 what assays are subject to interference from these hemoglobin 358 00:21:46.783 --> 00:21:49.783 variants. 359 00:21:50.016 --> 00:21:51.733 The next test used for 360 00:21:51.733 --> 00:21:55.116 diagnosis of diabetes is measurement of blood glucose. 361 00:21:57.100 --> 00:21:57.916 The specimen of 362 00:21:57.916 --> 00:22:00.950 choice for measurement of glucose in the clinical lab 363 00:22:01.266 --> 00:22:04.266 is from blood collected in a gray top tube. 364 00:22:04.966 --> 00:22:07.966 The gray top tube contains sodium fluoride, 365 00:22:08.233 --> 00:22:13.150 which acts as a glycolytic inhibitor, and it prevents the cells in the blood 366 00:22:13.150 --> 00:22:17.150 from utilizing glucose, which would falsely decrease the result 367 00:22:17.450 --> 00:22:20.450 if the sample remain on the cells too long. 368 00:22:20.916 --> 00:22:25.266 Glucose in these gray top tubes is stable for, about 24 hours. 369 00:22:26.000 --> 00:22:30.133 For measurement of glucose on glucometer is used for at home, 370 00:22:30.366 --> 00:22:33.650 monitoring or for quick screening in the clinic. 371 00:22:33.966 --> 00:22:37.633 They typically use whole blood, often from a fingerstick 372 00:22:38.500 --> 00:22:42.133 and then, continuous glucose monitors that are used by 373 00:22:42.133 --> 00:22:45.966 some patients actually measure glucose in the interstitial fluid, 374 00:22:46.783 --> 00:22:50.716 more and frequently urine can be measured. 375 00:22:51.316 --> 00:22:54.316 Glucose can be measured in the urine using a urine dipstick. 376 00:22:54.600 --> 00:22:56.683 But this method is pretty insensitive. 377 00:22:56.683 --> 00:22:59.116 So it's not used, for diagnosis at all. 378 00:23:01.700 --> 00:23:04.850 The sample type really matters when it comes to measuring glucose, 379 00:23:05.216 --> 00:23:08.350 whether it's capillary or whole blood versus plasma. 380 00:23:08.916 --> 00:23:12.133 And the reason for this is because glucose distributes 381 00:23:12.133 --> 00:23:15.133 to the water phase of cells and plasma. 382 00:23:15.733 --> 00:23:19.850 Therefore, the glucose concentration is higher in the plasma 383 00:23:19.850 --> 00:23:24.500 than the whole blood because red blood cells contain only about 80% water 384 00:23:24.650 --> 00:23:27.966 compared to 93% water in the plasma. 385 00:23:28.750 --> 00:23:32.083 In general, the estimation of whole blood glucose levels 386 00:23:32.083 --> 00:23:35.683 are usually 10 to 15% lower than plasma glucose alone. 387 00:23:36.466 --> 00:23:39.066 For example, 388 00:23:39.066 --> 00:23:41.716 if we have a plasma blood 389 00:23:41.716 --> 00:23:44.750 glucose of 100 MiGs per deciliter, 390 00:23:45.150 --> 00:23:49.850 that would be equivalent to about 80, 80, 88 MiGs per deciliter measured 391 00:23:49.850 --> 00:23:54.733 in a whole blood sample and 70 MiGs per deciliter in the red blood cells. 392 00:23:55.450 --> 00:24:00.650 The difference between these two, whole blood versus plasma also depends 393 00:24:00.650 --> 00:24:05.116 on the hematocrit concentration, or how much red blood cells there is. 394 00:24:05.566 --> 00:24:06.466 So, for example, 395 00:24:06.466 --> 00:24:11.050 a low hematocrit can result in a falsely elevated blood glucose level. 396 00:24:11.350 --> 00:24:15.400 And so when you're interpreting the result from the glucose measurement it's 397 00:24:15.400 --> 00:24:19.066 important to remember reference intervals will differ based on that sample type. 398 00:24:22.150 --> 00:24:25.100 The most common methods used for measurement of blood 399 00:24:25.100 --> 00:24:28.633 blood glucose concentrations are enzymatic methods. 400 00:24:29.116 --> 00:24:33.200 With photometric or AMP AMP parametric detection. 401 00:24:34.000 --> 00:24:38.766 The two enzymes used clinically or are HEXO kinase, which is the reference 402 00:24:38.766 --> 00:24:42.966 method for glucose measurement, as well as glucose oxidase. 403 00:24:43.850 --> 00:24:47.083 This image here just highlights that the various 404 00:24:47.083 --> 00:24:51.966 forms of enzyme based glucose sensors can take, various 405 00:24:51.966 --> 00:24:56.616 different forms from, invasive methods that require a blood stick 406 00:24:56.900 --> 00:25:01.266 or an implantable device to noninvasive methods that, collect, 407 00:25:01.816 --> 00:25:05.316 for example, collect sweat or tears. 408 00:25:08.316 --> 00:25:11.316 In the laboratory, the HEXO kinase method 409 00:25:11.450 --> 00:25:15.466 has been accepted as the reference method for glucose determination, 410 00:25:15.883 --> 00:25:18.883 and it's the most frequently, implemented method 411 00:25:18.883 --> 00:25:22.333 on automated analyzers that are found in the central laboratory. 412 00:25:23.083 --> 00:25:27.316 In this method, glucose is phosphorylated by HEXO kinase 413 00:25:27.316 --> 00:25:31.066 in the presence of ATP to form glucose six phosphate. 414 00:25:31.716 --> 00:25:36.133 The enzyme glucose six phosphate dehydrogenase converts the glucose six 415 00:25:36.133 --> 00:25:42.133 phosphate into six phosphate gluconate with nicotinic adenine 416 00:25:42.400 --> 00:25:46.783 dinucleotide, or NAD concurrently reduced to NAD, 417 00:25:47.866 --> 00:25:49.666 and every micromolar of 418 00:25:49.666 --> 00:25:53.566 glucose consume produces one micro mole of NAD, 419 00:25:54.516 --> 00:25:56.716 and that NAD absorbs light 420 00:25:56.716 --> 00:25:59.716 at 340 nanometers. 421 00:25:59.716 --> 00:26:02.716 So that's what's monitored in this assay. 422 00:26:03.133 --> 00:26:07.116 And the increase in absorbance is directly proportional 423 00:26:07.116 --> 00:26:10.116 to the glucose concentration in the specimen. 424 00:26:11.600 --> 00:26:14.750 The other enzyme used is glucose oxidase, 425 00:26:15.200 --> 00:26:19.033 and both laboratory base and point of care glucose measuring systems, 426 00:26:19.316 --> 00:26:23.200 have utilized the enzyme glucose oxidase. 427 00:26:23.600 --> 00:26:27.100 This enzyme catalyzes the oxidation of glucose 428 00:26:27.100 --> 00:26:30.100 to gluconate acid and hydrogen peroxide, 429 00:26:31.216 --> 00:26:33.350 and the reaction can be monitored 430 00:26:33.350 --> 00:26:36.350 for metrically or AMP parametrically, 431 00:26:36.466 --> 00:26:40.216 the consumption of oxygen or the production of hydrogen peroxide 432 00:26:40.716 --> 00:26:44.766 can be measured to estimate the amount of glucose present in. 433 00:26:44.766 --> 00:26:49.250 For the photometric assays, the system includes a second enzyme, 434 00:26:49.600 --> 00:26:52.600 peroxide base, as well as a chroma gene, 435 00:26:52.666 --> 00:26:56.466 and the change in that chroma gene changes to a colored product. 436 00:26:56.466 --> 00:27:01.333 When oxidized, the intensity of the color measured photometric 437 00:27:01.550 --> 00:27:04.550 is directly proportional to the glucose concentration. 438 00:27:05.083 --> 00:27:09.250 And, this reaction has been adapted for both automated measurement in the 439 00:27:09.250 --> 00:27:15.133 laboratory as well as point of care, test strips and glucose, reflectance meters, 440 00:27:16.900 --> 00:27:20.350 the consumption of oxygen and the production of hydrogen peroxide 441 00:27:20.350 --> 00:27:23.916 that results from that first reaction with glucose oxidase. 442 00:27:24.733 --> 00:27:27.733 Also allows an parametric measurement of glucose. 443 00:27:28.133 --> 00:27:31.900 The hydrogen peroxide formed, 444 00:27:31.900 --> 00:27:35.616 when glucose comes in contact with the glucose oxidase membrane, 445 00:27:35.950 --> 00:27:40.966 diffuses across the second membrane and is oxidized at the platinum electrode. 446 00:27:41.266 --> 00:27:44.116 And the current generated is proportional to the, 447 00:27:44.116 --> 00:27:47.116 glucose concentration. 448 00:27:49.183 --> 00:27:52.450 The last laboratory method for diagnosis of diabetes 449 00:27:52.450 --> 00:27:55.450 that we'll discuss is the oral glucose tolerance test. 450 00:27:57.550 --> 00:27:59.316 The oral glucose tolerance 451 00:27:59.316 --> 00:28:03.016 test evaluates how the body manages glucose after meal. 452 00:28:03.433 --> 00:28:08.350 It is used in both the screening for and diagnosis of diabetes, 453 00:28:08.650 --> 00:28:11.683 but it is not used in monitoring of the disease. 454 00:28:11.683 --> 00:28:14.650 Because you can imagine you don't want to give a diabetic 455 00:28:14.650 --> 00:28:17.650 a bunch of sugar, just to see how they respond to it. 456 00:28:18.450 --> 00:28:23.983 Although the procedures can vary between clinics, shown 457 00:28:23.983 --> 00:28:28.450 here are three common procedures for the oral glucose tolerance test. 458 00:28:28.816 --> 00:28:32.266 For example, a two hour or a glucose tolerance test, 459 00:28:32.783 --> 00:28:36.966 is comprised of two blood draws, and it may be used 460 00:28:36.966 --> 00:28:41.800 to diagnose diabetes or prediabetes in non-pregnant adults and children. 461 00:28:42.366 --> 00:28:46.816 And in this test, a baseline blood glucose is measured in the fasted state. 462 00:28:47.383 --> 00:28:51.733 And then the patient will have to consume a drink containing a specific amount 463 00:28:51.733 --> 00:28:54.766 of sugar, followed by another blood glucose 464 00:28:54.766 --> 00:28:57.850 measurement two hours after consumption of that drink 465 00:28:59.533 --> 00:29:00.666 during pregnancy. 466 00:29:00.666 --> 00:29:04.550 One format of the oral glucose tolerance test is a three hour 467 00:29:04.550 --> 00:29:07.750 test, as opposed to the two hour test I just described. 468 00:29:08.350 --> 00:29:11.766 And this is comprised of four blood draws. 469 00:29:11.766 --> 00:29:14.400 So they'll take one at fasting again. 470 00:29:14.400 --> 00:29:17.600 And then one at one, two and three hours 471 00:29:17.600 --> 00:29:21.200 post consumption of a glucose containing drink. 472 00:29:22.650 --> 00:29:27.550 And in all these tests, glucose collected in the blood draws is measured 473 00:29:27.550 --> 00:29:31.100 using one of the enzymatic reactions I just, described. 474 00:29:32.833 --> 00:29:34.400 If we, take a look 475 00:29:34.400 --> 00:29:38.800 at the expected glucose profile, over time, during an oral 476 00:29:38.800 --> 00:29:43.033 glucose tolerance, you can see that in a healthy individual. 477 00:29:43.033 --> 00:29:47.316 And the trace on the bottom, the initial fasting glucose is within 478 00:29:47.316 --> 00:29:52.250 normal limits, and the highest peak value is reached within an hour. 479 00:29:52.250 --> 00:29:56.716 And it doesn't exceed the renal threshold, highlighted by that dotted line. 480 00:29:57.550 --> 00:30:01.700 And that renal threshold is the ability of the kidney to reabsorb glucose. 481 00:30:01.700 --> 00:30:05.683 And it's typically around 160 to 180 makes per deciliter. 482 00:30:06.816 --> 00:30:09.950 And then in a normal individual, the fasting level is again 483 00:30:09.950 --> 00:30:15.466 reached by two to 2.5 hours in a diabetic fasting blood glucose. 484 00:30:15.466 --> 00:30:19.000 In a diabetic, the fasting blood glucose is elevated. 485 00:30:19.000 --> 00:30:22.183 You can see in both the moderate and severe diabetic 486 00:30:22.183 --> 00:30:25.183 that first time point is elevated compared to normal. 487 00:30:26.916 --> 00:30:30.350 And and then also the 488 00:30:30.350 --> 00:30:34.416 the peak value is reached one to 1.5 hours. 489 00:30:34.666 --> 00:30:37.183 And that peak value exceeds the renal threshold. 490 00:30:37.183 --> 00:30:40.450 So glucose will begin to be excreted in the urine at that point. 491 00:30:41.200 --> 00:30:45.066 And the most characteristic feature of diabetes on the oral 492 00:30:45.066 --> 00:30:49.150 glucose tolerance test is that the glucose does not return to fasting levels 493 00:30:49.150 --> 00:30:52.183 within two to 2.5 hours, so it still remains elevated. 494 00:30:55.000 --> 00:30:57.433 Vantages of doing an oral glucose tolerance test 495 00:30:57.433 --> 00:31:00.883 is that it has very high sensitivity for the diagnosis of, 496 00:31:00.883 --> 00:31:03.883 both prediabetes and diabetes. 497 00:31:04.016 --> 00:31:07.116 The sensitivity is about 81 to 93%, 498 00:31:07.783 --> 00:31:11.683 and it's particularly better at detecting early impairment. 499 00:31:11.683 --> 00:31:15.283 So, identifying those that are in prediabetes where they can 500 00:31:15.283 --> 00:31:19.066 maybe implement some lifestyle changes before they become full on diabetic. 501 00:31:21.250 --> 00:31:21.766 There are also 502 00:31:21.766 --> 00:31:25.400 several limitations of this oral glucose tolerance test. 503 00:31:25.866 --> 00:31:29.233 And that's one is it's very time consuming. 504 00:31:29.233 --> 00:31:32.616 It requires the patients to come in fasted, drink this, drink. 505 00:31:32.616 --> 00:31:34.966 That probably is not it doesn't taste the best. 506 00:31:34.966 --> 00:31:38.650 And then they have to wait two hours before they can get their blood 507 00:31:38.650 --> 00:31:40.166 drawn again. 508 00:31:40.166 --> 00:31:43.333 It requires them to adhere to that pretest fast. 509 00:31:43.866 --> 00:31:48.283 And it can be influenced by stress, illness or different medications. 510 00:31:48.766 --> 00:31:53.350 And lastly, improper handling or storage of the sample can skew results 511 00:31:53.350 --> 00:31:56.900 as glucose is readily metabolized by cells in the sample. 512 00:31:59.383 --> 00:32:01.866 So now that I've gone through the methods to diagnose 513 00:32:01.866 --> 00:32:05.166 diabetes, let's discuss the cutoffs used for each one. 514 00:32:07.300 --> 00:32:10.266 The first test I talked about was the hemoglobin A1. 515 00:32:10.266 --> 00:32:14.433 C so a normal individual 516 00:32:14.433 --> 00:32:18.583 will have a hemoglobin A1 C of less than 5.7%. 517 00:32:19.400 --> 00:32:24.850 Prediabetes is defined by a range of 5.7 to 6.4%. 518 00:32:24.850 --> 00:32:27.183 So this is where you have elevated glucose 519 00:32:27.183 --> 00:32:31.100 but not quite elevated enough to be considered a diabetes. 520 00:32:31.550 --> 00:32:35.416 And a hemoglobin A1, C greater than or equal to 6.5% 521 00:32:35.683 --> 00:32:38.083 is consistent with diabetes. 522 00:32:38.083 --> 00:32:40.516 And sufficient for the diagnosis. 523 00:32:42.250 --> 00:32:44.016 The next test used for 524 00:32:44.016 --> 00:32:47.350 diagnosis of diabetes is a fasting plasma glucose. 525 00:32:47.900 --> 00:32:51.283 In a normal individual, fasting plasma glucose should be less 526 00:32:51.283 --> 00:32:53.300 than 100 makes per deciliter. 527 00:32:53.300 --> 00:32:58.250 In a pre-diabetic, it would be about 100 to 125 MCs per deciliter. 528 00:32:58.250 --> 00:33:02.416 And then diabetes is diagnosed with a fasting plasma glucose of greater 529 00:33:02.416 --> 00:33:05.416 than or equal to 126 meals per deciliter. 530 00:33:06.700 --> 00:33:08.950 It's important to note, random 531 00:33:08.950 --> 00:33:12.650 glucose can be used to aid in the diagnosis. 532 00:33:13.116 --> 00:33:16.750 And in a diabetic, a random glucose greater than or equal 533 00:33:16.750 --> 00:33:20.350 to 200 makes per deciliter is consistent with diabetes. 534 00:33:21.616 --> 00:33:24.850 And then lastly, I discussed that oral glucose tolerance tests. 535 00:33:25.366 --> 00:33:30.016 And particularly looking at the two hour measurement, a normal individual 536 00:33:30.016 --> 00:33:33.850 would have a blood glucose of less than 140 makes per deciliter 537 00:33:34.216 --> 00:33:39.800 at the two hour time point, whereas prediabetes is defined by 140 299 538 00:33:39.800 --> 00:33:43.900 MCs per deciliter, and then diabetes can be diagnosed with a, 539 00:33:43.983 --> 00:33:48.200 blood glucose of greater than or equal to 200 makes per deciliter. 540 00:33:49.366 --> 00:33:51.733 Another important note to keep in mind 541 00:33:51.733 --> 00:33:55.850 is that the diagnosis ideally should include two abnormal results. 542 00:33:56.233 --> 00:34:00.350 It can be from two different tests taken, on the same day. 543 00:34:00.350 --> 00:34:03.350 So the a1 C and the fasting plasma glucose. 544 00:34:03.583 --> 00:34:07.633 Or it can be from the same test taken at two different times. 545 00:34:08.666 --> 00:34:11.916 So now that we've discussed the laboratory methods used to diagnose 546 00:34:11.916 --> 00:34:16.083 diabetes, we'll talk about how they are treated once diagnosed. 547 00:34:17.383 --> 00:34:21.733 There are four major components to the treatment of diabetes. 548 00:34:22.000 --> 00:34:24.166 The first is insulin. 549 00:34:24.166 --> 00:34:27.033 All individuals with type one diabetes 550 00:34:27.033 --> 00:34:30.283 need to take insulin every day, particularly with meals. 551 00:34:30.816 --> 00:34:34.633 And then only some people with type two diabetes will require this medication. 552 00:34:34.633 --> 00:34:38.533 And remember, insulin, helps lower blood glucose 553 00:34:38.533 --> 00:34:42.316 by facilitating, uptake of glucose into the cells. 554 00:34:44.050 --> 00:34:44.833 There are also several 555 00:34:44.833 --> 00:34:48.550 medications that can be used, particularly for type two diabetics. 556 00:34:48.900 --> 00:34:53.683 They may take a daily cocktail of one or more medications in addition to, 557 00:34:53.683 --> 00:34:57.983 sometimes needing insulin to help keep their blood sugar in a healthy range. 558 00:34:58.166 --> 00:35:02.750 Self-monitoring is another, critical component to diabetes care. 559 00:35:03.250 --> 00:35:06.166 Treatment really starts at home, where blood glucose 560 00:35:06.166 --> 00:35:09.166 should be tested every day, multiple times per day. 561 00:35:09.533 --> 00:35:12.983 And based on the glucose levels, the patients can then adjust, 562 00:35:13.233 --> 00:35:15.083 what and when to eat. 563 00:35:15.083 --> 00:35:17.666 And for type one diabetes, this also helps determine 564 00:35:17.666 --> 00:35:20.666 how much insulin they need to inject. 565 00:35:20.700 --> 00:35:24.166 And the last major component is diet and exercise. 566 00:35:24.166 --> 00:35:28.216 So although type one diabetes cannot be managed with these lifestyle changes, 567 00:35:28.733 --> 00:35:31.433 eating a healthy diet and regularly exercising 568 00:35:31.433 --> 00:35:35.333 can provide big benefits to those with, type two diabetes. 569 00:35:36.383 --> 00:35:36.683 So in 570 00:35:36.683 --> 00:35:40.916 conclusion, diabetes is a group of metabolic disorders 571 00:35:40.916 --> 00:35:43.916 characterized by high levels of sugar in the blood. 572 00:35:44.783 --> 00:35:48.950 A diagnosis requires measurement of fasting plasma glucose, 573 00:35:49.383 --> 00:35:53.583 hemoglobin A1, C, and or the oral glucose tolerance tests. 574 00:35:53.900 --> 00:35:54.833 And again, ideally, 575 00:35:54.833 --> 00:35:58.500 you should have two different results that support a diagnosis of diabetes. 576 00:35:59.283 --> 00:36:02.283 And then treatment requires regular glucose monitoring 577 00:36:02.600 --> 00:36:06.300 and may include insulin or different therapeutics designed 578 00:36:06.300 --> 00:36:11.150 to increase insulin secretion or decrease hepatic, glucose production. 579 00:36:11.850 --> 00:36:15.383 And again, diet and lifestyle choices are also very important factors 580 00:36:15.383 --> 00:36:18.933 in successful treatment, particularly for, type two diabetes. 581 00:36:19.500 --> 00:36:20.666 I'd like to thank you 582 00:36:20.666 --> 00:36:24.500 for your attention and hope this was a very informative presentation. 583 00:36:24.500 --> 00:36:25.000 Thank you.