The physiologic replacement of insulin. An elusive goal.
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Diabetes Mellitus↗
Biomedical subjects
B Zinman
Publications and source records attributed to B Zinman.
Determination and kinetic analysis of non-insulin mediated glucose uptake in type 1 (insulin-dependent) diabetes mellitus.
In man, total glucose uptake is the sum of insulin mediated glucose uptake and non-insulin mediated glucose uptake. The later pathway has not been examined in Type 1 (insulin-dependent) diabetes mellitus. In order to assess non-insulin mediated glucose uptake in Type 1 diabetes, we measured steady-state rates of glucose uptake during glucose clamps at 5.27, 9.71 and 12.5 mmol/l using low (0.25 mU.kg-1.min-1), intermediate (0.75 mU.kg-1.min-1) and high (1.50 mU.kg-1.min-1) insulin infusion rates in 10 subjects with Type 1 diabetes. For insulin infusion rates of 0.25, 0.75 and 1.50 mU.kg-1.min-1 as plasma glucose rose from 5.27 to 9.71 mmol/l, total glucose uptake increased by 35, 43 and 52 percent respectively (p less than 0.05 for each insulin infusion rate). For all three insulin infusion rates, there was no significant increase in total glucose uptake as plasma glucose increased from 9.71 to 12.5 mmol/l. At each glycaemic level, glucose uptake correlated significantly with plasma free insulin (r = 0.81, p less than 0.01 at 5.71 mmol/l; r = 0.84, p less than 0.01 at 9.71 mmol/l; r = 0.73, p less than 0.02 at 12.5 mmol/l). Linear regression analysis to a point corresponding to plasma free insulin equalling zero, yielded values for non-insulin mediated glucose uptake (mmol.kg-1.min-1) of 0.11, 0.14, 0.18 at plasma glucose of 5.27, 9.7 and 12.5 mmol/l respectively. Thus, increasing plasma glucose concentrations were associated with increasing rates of non-insulin mediated glucose uptake. For each insulin infusion rate used, the percent of total glucose uptake accounted for by non-insulin mediated glucose uptake remained independent of plasma glucose concentration, but decreased as insulin infusion rate increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The effects of SMS 201-995 (sandostatin) on metabolic profiles in insulin-dependent diabetes mellitus.
GH has been implicated in the pathophysiology of various acute and chronic complications of diabetes mellitus. As a consequence, there has been a great deal of interest in developing methods for suppressing GH secretion in diabetes. SMS 201-995 is a long-acting somatostatin analog which inhibits the secretion of numerous hormones, including GH. To determine the metabolic and hormonal responses to SMS 201-995 independent of endogenous insulin suppression, we studied six patients with insulin-dependent diabetes mellitus while they received 150 micrograms SMS 201-995, sc, daily for an 8-week period. This treatment resulted in no change in 24-h glucose profiles, although the mean insulin dose decreased by 19%, while hemoglobin A1c decreased significantly (0.084 +/- 0.023 to 0.067 +/- 0.011, P = 0.04). The 24-h profiles of blood lactate, plasma free insulin, glucagon, FFA, blood glycerol, and beta-hydroxybutyrate were unchanged, whereas that of blood alanine increased significantly (7.8 +/- 0.4 to 10.6 +/- 0.9 mmol/L.h; P = 0.01). GH secretion declined in five of the six patients; the mean values before and during SMS 201-995 treatment were 102 +/- 23 and 68 +/- 12 micrograms/L.h, respectively (P = NS), for the six patients. [In the five patients in whom GH secretion declined, the mean values before and during SMS 201-995 treatment were 115 +/- 23 and 63 +/- 14 micrograms/L.h, respectively (P = 0.01).] These results suggest that SMS 201-995 may be administered to patients with insulin-dependent diabetes mellitus without a deleterious effect on metabolic control.
Adult↗
Hormonal and metabolic responses during coronary artery bypass surgery: role of infused glucose.
Anesthesia, surgery, and hypothermia are conventionally considered the major stress factors in the metabolic and hormonal responses to cardiac surgery. We compared these responses in 14 nondiabetics during and for 24 h after coronary artery bypass surgery; 8 received cardioplegic solutions (C+), and 6 did not (C-). The mean intraoperative glucose load in C+ was 106 g compared to 32 g in C-; postoperatively both groups received 50 g. Marked hyperglycemia (31.8 +/- 4.8 mmol/L) occurred during hypothermia in C+, but dropped to 18.9 mmol/L before surgery ended and to 11.2 +/- 1.1 mmol/L by 2 h postop. In contrast, C- showed constant mild hyperglycemia of 8.3-9.8 mmol/L throughout, significantly less than C+ until 1 h postop. Insulin was suppressed by 55% only during hypothermia, peaking with rewarming in C+ at 2,849 +/- 911 vs. 639 +/- 251 pmol/L in C- (P less than 0.05); as with glycemia, values were comparable after 2 h postop. The pancreatic beta-cell thus responded to hyperglycemia during restoration of normothermia, resulting in a rapid decline in glycemia. This occurred despite elevations in antiinsulin factors in both groups; GH was 14 +/- 4 micrograms/L, cortisol was 607 +/- 38.6 nmol/L, norepinephrine was 11.5 +/- 3.7 nmol/L, epinephrine was 13,863 +/- 3,875 pmol/L, and FFA were 0.36 +/- 0.05 g/L. Early postop, a secondary rise in stress hormones occurred in both groups. Maximal cortisol values were at 4 h (1,186 +/- 140 nmol/L) and peaks of norepinephrine (6.50 +/- 1.66 nmol/L), epinephrine (7,969 +/- 3,602 pmol/L), and FFA (0.27 +/- 0.03 g/L) occurred. The only significant glucagon elevation was at 24 h (C+, 464 +/- 53 ng/L; C-, 350 +/- 241 ng/L; P less than 0.02), Thus, 1) many metabolic responses during coronary artery bypass surgery are influenced by the glucose-containing cardioplegic solution; 2) hypothermia suppresses insulin secretion, but it responds thereafter despite marked elevations of catecholamines, and is associated with decreasing glycemia despite elevated antiinsulin factors; 3) a lesser but highly significant stress response corresponds to awakening from anesthesia; and 4) glucagon plays a minor role in intraoperative hyperglycemia; the rise at 24 h is unexplained.
Aged↗
Triglyceride-rich lipoprotein metabolism during acute hyperinsulinemia in hypertriglyceridemic humans.
Chronic endogenous hyperinsulinemia is associated with increased rates of triglyceride production in humans. The effect of acute exogenous hyperinsulinemia on triglyceride production was studied in seven hypertriglyceridemic men before and during six hours of hyperinsulinemic-euglycemic clamping, and in two men before and during six hours of hyperinsulinemic-hyperglycemic clamping. Apparent triglyceride production rates were assessed qualitatively by examining the rate of decline of 3H-glycerol-labeled plasma triglyceride specific activity in the preclamp period, and again when a new steady state had occurred, during the final three hours of the clamp. During the euglycemic (91.2 +/- 3.0 mg glucose/dL plasma) clamps, plasma insulin levels were increased by 700% (0.76 +/- 0.12 to 5.3 +/- 0.29 ng/mL, P less than .001) and plasma glucagon levels decreased by 19%, compared with baseline. The apparent triglyceride production rate did not increase in five of six men during the euglycemic-hyperinsulinemic clamp, or in either man during the hyperglycemic-hyperinsulinemic clamp. During the clamp period the triglyceride declined in the plasma by 23.4 +/- 3.1%; and the apolipoprotein B by 10.5 +/- 1.5%. Hyperinsulinemia with euglycemia was also associated with a decline in the ratio of triglyceride to apolipoprotein B in the triglyceride-rich lipoproteins. This was more pronounced in very low density lipoprotein (VLDL) than in intermediate density lipoprotein (IDL). In this study, hyperinsulinemia led to a decrease in the plasma glucagon concentration. This decrease was positively correlated with the decrease in the slope of the triglyceride specific activity v time curve. Hence, the changes in triglyceride production were not due to an increase in plasma glucagon concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
The relationship of cardiac diastolic dysfunction to concurrent hormonal and metabolic status in type I diabetes mellitus.
The presence of diabetic cardiomyopathy and its relationship to concurrent hormonal and metabolic status have not been defined in patients with uncomplicated type I diabetes mellitus. Accordingly, radionuclide left ventricular angiograms and simultaneous metabolic profiles were obtained in 8 type I diabetic patients who had no major diabetic complications and in 11 normal subjects. Occult coronary artery disease was excluded by electrocardiogram exercise testing. Hemodynamics and systolic function did not differ between the groups. However, the peak filling rate (PFR; end-diastolic volumes per s) was less in the diabetic patients at rest [mean, 4.1 +/- 0.2 (+/- SE) vs. 4.8 +/- 0.2; P less than 0.05] and during aerobic (6.8 +/- 0.2 vs. 8.30 +/- 0.3; P less than 0.01) and anaerobic exercise (8.8 +/- 0.3 vs. 9.8 +/- 0.4; P less than 0.05). The time to PFR was prolonged in the diabetic patients at rest (174 +/- 10 vs. 133 +/- 7 ms; P less than 0.01) and during anaerobic exercise (126 +/- 5 vs. 103 +/- 6 ms; P less than 0.01). Plasma glucose and insulin levels were elevated in the diabetic patients at rest and during exercise. Otherwise, the metabolic and hormonal levels did not differ between the groups. In the diabetic patients, no single metabolic or hormonal parameter correlated with PFR or time to PFR. Impairment of diastolic filling also did not correlate with level of glycosylated hemoglobin or duration of diabetes. The alteration in diastolic filling present in type I diabetic patients who have no other diabetic complications may represent the earliest functional effect of diabetic cardiomyopathy.
Adult↗
Counterregulatory hormone responses preserved after long-term intravenous insulin infusion compared to continuous subcutaneous insulin infusion.
The counterregulatory hormone responses of cortisol, growth hormone, glucagon, epinephrine, norepinephrine, and dopamine to a fixed hypoglycemic stimulus (50 mg/dl for 1 h) were studied in five type I (insulin-dependent) diabetic subjects during conventional insulin therapy (CT), after 3 mo of continuous subcutaneous insulin infusion (SC), and after 3 mo of continuous intravenous insulin infusion (IV). During the two infusion periods, the overall mean levels of preprandial blood glucose (116 +/- 6 SC vs. 114 +/- 5 mg/dl IV) and glycosylated hemoglobin (6.1 +/- 2 SC vs. 5.9 +/- 2% IV) were virtually identical, but there were more hypoglycemic episodes and greater variability of preprandial blood glucose levels during SC than with IV. During the last 30 min of the hypoglycemic clamps, the mean levels of epinephrine and cortisol were significantly lower after 3 mo of SC (epinephrine, 268 +/- 80 pg/ml; cortisol, 14 +/- 1 microgram/dl) than with both CT (epinephrine 485 +/- 80 pg/ml; cortisol, 20 +/- 2 micrograms/dl) and IV (epinephrine, 443 +/- 62 pg/ml; cortisol, 19 +/- 2 micrograms/dl)(P less than .05). The mean growth hormone level was significantly (P less than .05) lower after SC (37 +/- 9 ng/ml) than after IV (79 +/- 12 ng/ml), but it did not reach statistical significance compared with CT (66 +/- 12 ng/ml). The mean glucagon, dopamine, and norepinephrine levels during the same period of hypoglycemia were not different when all treatment regimens were compared. We conclude that intensified insulin therapy with SC leads to significant blunting of the counterregulatory hormone response to hypoglycemia, whereas IV does not.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of weight loss in massive obesity on insulin and C-peptide dynamics: sequential changes in insulin production, clearance, and sensitivity.
In massively obese patients hyperinsulinemia and insulin insensitivity usually improve with weight loss. To clarify the mechanism of these reversible abnormalities eight nondiabetic massively obese patients were studied before and at intervals (3 months and 1 yr) after weight loss following gastroplasty. Insulin dynamics were studied during the hyperglycemic clamp (change in glucose, 7 mmol L-1 for 2 h) by measuring the area under the insulin and C-peptide response curves, representing, respectively, systemic insulin response and insulin production. Compared to lean age-matched normal subjects the massively obese patients had the expected fasting hyperinsulinemia and an exaggerated insulin response (P less than 0.05). Within 3 months and after an approximately 20% weight loss, they had a marked reduction in the systemic insulin response but no change in the C-peptide response. Therefore, the reduction in insulin response was due to enhanced hepatic insulin clearance rather than reduced insulin production. Thus, the liver serves a gate-keeping role in regulating the systemic insulin response to a glucose challenge. With additional weight loss of 14% and then weight maintenance, insulin clearance was further increased, and a reduction in insulin production became evident, since the C-peptide response was reduced. Exogenous insulin clearance was measured using the euglycemic clamp technique before and after weight loss. Insulin clearance was initially lower in the massively obese patients compared to that in the normal subjects (P less than 0.05) and increased toward normal with weight loss (P less than 0.05). Similarly, insulin sensitivity, as measured by the ratio of glucose metabolised per U endogenous insulin, normalized with weight loss and weight maintenance. Thus, after significant weight loss followed by weight maintenance at a reduced, but not ideal, level, insulin clearance, production, and sensitivity all reverted to normal. These findings suggest that adipose mass per se may not be exclusively responsible for altered insulin and glucose dynamics in obesity and that additional factors associated with obesity, such as nutrient load, adipose distribution, fat cell size, or fatty acid flux, play a contributing role.
Adult↗
Biosynthetic human insulin improves postprandial glucose excursions in type I diabetics.
To determine if the more rapid absorption of subcutaneously administered human insulin, as compared with animal insulin, would result in an improved postprandial metabolic response, ten persons with type I diabetes mellitus were studied during a fixed meal. Plasma glucose and insulin concentrations were compared after subcutaneous injections of 0.2 U/kg body weight of regular biosynthetic human insulin or regular purified pork insulin in a double-blind randomized crossover trial. Meal glycemic excursions improved after the administration of biosynthetic human insulin, when compared with purified pork insulin (p less than 0.05 at 150, 180, and 210 minutes postprandially). Serum free immunoreactive insulin concentrations were significantly higher after injections of biosynthetic human insulin, and the rate of incremental rise during the first 30 minutes was also greater. Insulin antibody studies showed a strong negative correlation between peak insulin levels and the association constant for the high-affinity-binding insulin antibodies. We conclude that biosynthetic human insulin is more rapidly absorbed after subcutaneous injection than is purified pork insulin, a characteristic that results in improved postprandial metabolic control.
Absorption↗
Factors affecting the urinary excretion of albumin in insulin-dependent diabetes.
To determine the specificity of the urine excretion of albumin as a measure of glomerular permeability in early insulin-dependent diabetic nephropathy, the effect of variable glomerular filtration and urine flow rates on albumin, beta 2-microglobulin excretion, and the fractional renal clearance of neutral dextran (Stokes Einstein Radius 24-46 A) was examined. Five insulin-dependent diabetic subjects with normal glomerular permeability (albumin excretion less than 30 micrograms/min) and one with elevated albumin excretion (195 micrograms/min) were studied pre and post strict glucose control with constant subcutaneous insulin infusion for 7 days. The albumin excretion in the 5 subjects never exceeded 30 micrograms/min during wide variations in glomerular filtration and urine flow rates. A positive correlation between beta 2-microglobulin excretion and urine flow (r = 0.81), and glomerular filtration (r = 0.77) rates was observed. In contrast, albumin excretion showed no correlation, indicating different factors affect the excretion rate of albumin and beta 2-microglobulin. Therefore, elevated albumin excretion (greater than 30 micrograms/min) in insulin-dependent diabetes is due to increased glomerular permeability and not changes in glomerular filtration and urine flow rates, and the albumin/ beta 2-microglobulin ratio may not be a valid indicator of changing glomerular permeability. The fractional neutral dextran clearances remained unchanged with variation in glomerular filtration and urine flow rates. The sieving curve was identical in all subjects for neutral dextran 40 A, the size of albumin, suggesting that reduced glomerular charge selectivity may contribute to increased albuminuria in progressive diabetic glomerulosclerosis.
Adult↗
Changes in insulin sensitivity and clearance in anorexia nervosa.
Anorexia nervosa (AN) is a state of self-induced malnutrition characterized by a marked pursuit of thinness and the fear of obesity. Although low fasting blood glucose and insulin have been demonstrated, there is contradictory data on insulin sensitivity and a lack of information about insulin metabolism and its metabolic effects in AN. Insulin sensitivity, kinetics, and metabolic effects were measured using the euglycemic clamp in nine females with AN (age 25.2 +/- 1.9 years and 70.6 +/- 2.2% ideal body weight), and the results compared with seven female normal controls (NC) (age 23.6 +/- 1.0 years and 92.7 +/- 2.5% ideal body weight). Fasting plasma glucose (FPG), immunoreactive insulin (IRI), and C-peptide were significantly lower in AN as compared to NC (84.3 +/- 1.5 v 91.5 +/- 1.7 mg dL-1, 9.3 +/- 1.0 v 13.5 +/- 1.4 microU mL-1, and 0.26 +/- 0.03 v 0.41 +/- 0.02 pmol mL-1) (P less than 0.05). During the glucose clamp, the glucose metabolized (M), the metabolic clearance rate of glucose (MCRg), and the glucose metabolized per unit of insulin (M/I ratio) were all higher in AN as compared to NC (M, 8.7 +/- 1.2 v 6.9 +/- 0.6 mg min-1 kg-1; MCRg, 9.9 +/- 1.5 v 7.4 +/- 0.6 mL min-1 kg-1; M/I ratio, 8.6 +/- 1.6 v 5.0 +/- 0.3 mg min-1 kg-1/microU mL-1 X 100), but only the M/I ratio attained statistical significance (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxybutyric Acid↗
Effects of massive obesity on insulin sensitivity and insulin clearance and the metabolic response to insulin as assessed by the euglycemic clamp technique.
Insulin sensitivity was studied in nine nondiabetic massively obese patients (one male and eight females ages 39.0 +/- 2.7 years, body mass index 47.1 +/- 1) by the euglycemic clamp technique (40 microU/m2/min) and compared to seven lean control subjects (three males and three females, ages 34.8 +/- 2.5 years, body mass index 23 +/- 1.1). Fasting plasma glucose, immunoreactive insulin, and C-peptide concentrations were higher in the massively obese patients than in the controls (P less than 0.025). Following exogenous insulin infusion, immunoreactive glucagon and C-peptide concentrations decreased similarly in the massively obese patients and controls, indicating normal sensitivity of the alpha and beta cell to insulin. Glucose uptake (M) expressed either as mg X min-1 of fat free mass was significantly reduced in the massively obese patients compared to the controls (P less than 0.001). Similarly, the M/I ratio (glucose uptake per unit of insulin) was significantly reduced in the massively obese patients (P less than 0.001). Free fatty acids and glycerol concentrations measured in the fasting state were significantly elevated in the massively obese patients (free fatty acids 678 +/- 51 v 467 +/- 55 mumol/L, P less than 0.05; glycerol 97 +/- 9 v 59 +/- 11 mumol/L, P less than 0.02). The effects of insulin on antilipolysis was assessed by measuring the reductions in free fatty acids and glycerol concentration during the glucose clamp study. Although the absolute levels remained higher in the massively obese patients, inhibition of lipolysis was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxybutyric Acid↗
Effect of exercise on the pancreatic polypeptide response to food in man.
Modest elevations in pancreatic polypeptide (PP) have been observed during exercise while fasting. To determine whether the PP response to a meal is similarly affected by exercise, seven healthy subjects were studied on two occasions. First, the postprandial PP response was determined during rest and then compared to a meal which was subsequently followed by a 45 min period of moderate exercise. Postprandial exercise significantly (P less than 0.01) enhanced the plasma PP response to peak levels of 182 +/- 22 pM versus 85 +/- 22 pM at rest. Concomitantly the plasma glucose fell to a nadir of 84 +/- 4 mg/dl which was significantly (P less than 0.01) below the rest level of 129 +/- 8 mg/dl. Although the rise in PP paralleled the fall in glucose, there was little relationship (r = 0.27) between the incremental changes in these two parameters. Thus, exercise is a natural setting which augments the plasma PP response to a meal. The mechanism may be related to the enhanced cholinergic vagal activity associated with the attendant fall in glycemia.
Adult↗
The metabolic response to the euglycemic insulin clamp in type I diabetes and normal humans.
The euglycemic insulin clamp has been utilized extensively to measure in vivo tissue sensitivity to insulin under various circumstances. Insulin sensitivity is determined from the amount of glucose metabolized under steady state conditions. To assess the effect of abnormalities in other insulin responsive metabolic pathways on glucose metabolism and thus insulin sensitivity as measured by the glucose clamp, the concentration of lactate, pyruvate, 3-hydroxybutyrate, glycerol, alanine, and free fatty acids were measured at baseline and during a two-hour euglycemic clamp in 13 nonobese subjects with type I diabetes. The observed responses were compared to 11 normal controls. Insulin sensitivity as measured by M (glucose metabolized), MCRg (metabolic clearance of glucose), and M/I ratio (glucose metabolized per unit insulin) were all significantly decreased in the diabetic subjects (P less than 0.005). Free fatty acids (FFA) and 3-hydroxybutyrate were significantly elevated at baseline in the diabetic subjects (P less than 0.05) and decreased significantly at 60 and 120 minutes in both groups. Baseline blood pyruvate and lactate concentrations were similar in the control and diabetic subjects. Pyruvate increased significantly at 60 minutes in both groups (P less than 0.05) and returned to baseline in the control subjects but remained elevated at 120 minutes in the diabetic subjects (P less than 0.001). Lactate increased similarly in both groups and remained elevated at 60 and 120 minutes. In summary, insulin sensitivity as assessed by the euglycemic insulin clamp is decreased in type I diabetes. However, specific differences in the concentration of several other metabolites both at baseline and in response to hyperinsulinemia were also identified in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxybutyric Acid↗
Diabetes and exercise.
The abnormal metabolic responses to exercise in insulin-dependent diabetes are in great part related to abnormal circulating plasma insulin concentrations. Exercising during relative insulin deprivation results in an increase in glycemia and ketosis. Exercise during insulin excess results in inhibition of hepatic glucose production and accelerated muscle glucose utilization and results in hypoglycemia. These responses can be significantly improved when insulin is administered more appropriately, as is the case with insulin infusion pumps. Self blood glucose monitoring before, during, and after exercise can provide important information that can be used to optimize the metabolic response to exercise in individual patients. A better understanding of the metabolic response to exercise in patients with diabetes will serve as the basis for developing specific recommendations to enable these individuals to have the freedom to take part in all forms of exercise with minimal restriction. However, the demonstration that exercise will have a long-term beneficial effect on the metabolic control of diabetes or prevent the development of the complications of diabetes remains to be established.
Diabetes Mellitus, Type 1↗
How laboratory dogs accommodate meals of different size but similar composition.
Healthy laboratory dogs appear to absorb a mixed meal from the gut at a constant rate. This rate is apparently not affected by meal size. If this is the case, then duration of absorption should depend on total or integrated meal size, whereas metabolite and hormonal levels would be independent of the number of feedings. To explore these hypotheses further, we compared the metabolite and hormonal responses with a single mixed meal and one divided in two halves, provided in two feedings 4 h apart. We detected no effect of the second meal in the metabolic response levels of glucose, lactate, pyruvate, alanine, free fatty acids, or 3-hydroxybutyrate or the hormonal responses of insulin, pancretic glucagon, gastrin, or secretin. Only minor differences were detectable in the hormonal response levels of pancreatic polypeptide, gastric inhibitory peptide, and enteroglucagon, consistent with a response to a second meal. We conclude that the observed change in circulating metabolite or hormone concentration is independent of the size of meal eaten, but the duration of the excursion depends on meal size. Thus, during the bulk phase of nutrient uptake, the absorption mechanism of the laboratory dog appears to be saturated.
Amino Acids↗
An evaluation of factors associated with proliferative diabetic retinopathy.
Many individual factors have been related to development of proliferative diabetic retinopathy. To evaluate possible interactions among these, a constellation of variables were studied in 22 patients with long duration of insulin-dependent diabetes mellitus for greater than 25 years, with minimal background diabetic retinopathy, and compared to 27 patients with insulin-dependent diabetes mellitus for a variable duration, but with bilateral proliferative retinopathy. The patients were compatible in age at onset of diabetes (12 +/- 2 in proliferative retinopathy group vs 12 +/- 1 yr in the background retinopathy group). Following initial standard statistical analyses, data were further analysed using Logistic Regression Analysis. In the proliferative retinopathy group males were more prevalent (2.9:1), and patients were treated with larger insulin doses (0.86 +/- 0.07 vs 0.59 +/- 0.04 U/Kg B.W., p less than 0.001). Systemic hypertension and neuropathy were more prevalent (p less than 0.02 and less than 0.004 respectively), and diastolic blood pressure was higher (87 +/- 3 vs 75 +/- 2, p less than 0.01). In the same group diet was higher in carbohydrate and the ratio of polyunsaturated to saturated fats was lower (p less than 0.03, less than 0.05 respectively). HbA1 was higher (0.127 +/- 0.004 vs 0.110 +/- 0.004%, p less than 0.004), but the mean of all available plasma glucose values was not different. Impaired renal function expressed by higher BUN, serum creatinine, and urinary protein and lower creatinine clearance was observed. Nerve conduction parameters were more significantly impaired and plasma triglycerides were higher (1.74 +/- 0.2 vs 0.85 +/- 0.1 mmol/l, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Changes in blood amino acids account for the insulin and glucagon responses to mixed meals in dogs.
The relationships between changes in the plasma levels of immunoreactive insulin (IRI) and glucagon (IRG) in response to the postprandial increments of circulating amino acids were studied under normal physiological conditions in healthy dogs. In the presence of a unique postprandial physiological euglycemic "glucose clamp" which occurs in these dogs, plasma IRG rose to an earlier peak than IRI and both remained elevated for 16-19 hr. Amino acid (AA) profiles also showed postprandial incremental responses for up to 16 hr. Multiple correlation analyses indicated that only branched chain AAs were significantly correlated with IRI profiles and were devoid of a relationship to IRG. Similarly, only ornithine, lysine and glycine were significantly correlated with IRG profiles and devoid of a relationship to IRI. The significance of individual IRG stimulating effects of alanine and arginine were masked by other amino acid interactions, as significant intercorrelation was found among all 13 amino acids. Two equations were derived from the multiple regression analysis accounting for the postprandial time course of changes in IRI and IRG levels with only 5 amino acid concentrations: (1) (delta IRI) = 0.37 (delta Leu) -0.45(delta His), and (2) (delta IRG) = 0.55(delta Orn) + 0.37(delta Gly) -0.69 (delta Ser). These observations confirm the physiologic role in islet hormone secretion of the postprandial increments in circulating amino acids in the absence of glycemic change.
Amino Acids↗