[Acute and chronic complications of diabetes secondary to pancreatopathies].
Explore the source record for details and available documents.
Acute Disease↗
Biomedical subjects
S Del Prato
Publications and source records attributed to S Del Prato.
[Plurimetabolic syndrome: association of diabetes, dyslipidemia, and arterial hypertension].
Explore the source record for details and available documents.
Diabetes Mellitus↗
Effect of sustained physiologic hyperinsulinaemia and hyperglycaemia on insulin secretion and insulin sensitivity in man.
Two study protocols to examine the effects of chronic (72-96 h) physiologic euglycaemic hyperinsulinaemia (+ 72 pmol/l) and chronic hyperglycaemic (+ 1.4 mmol/l) hyperinsulinaemia (+ 78 pmol/l) on insulin sensitivity and insulin secretion were performed in 15 healthy young subjects. Subjects received a three-step euglycaemic insulin (insulin infusion rates = 1.5, 3, and 6 nmol.kg-1.min-1) clamp and a hyperglycaemia (6.9 mmol/l) clamp before and after chronic insulin or glucose infusion. Following 4 days of sustained euglycaemic hyperinsulinaemia whole body glucose disposal decreased by 20-40%. During each insulin clamp step, the defect in insulin action was accounted for by impaired non-oxidative glucose disposal (p < 0.01). Chronic euglycaemic hyperinsulinaemia did not alter insulin-mediated suppression of hepatic glucose production. Following insulin infusion the ability of hyperglycaemia to stimulate insulin secretion was significantly diminished. Following 72 h of chronic glucose infusion (combined hyperglycaemic hyperinsulinaemia), there was no change in whole body glucose disposal. However, glucose oxidation during each insulin clamp step was significantly increased and there was a reciprocal decline in non-oxidative glucose disposal by 25-39% (p < 0.01); suppression of hepatic glucose production by insulin was unaltered by chronic hyperglycaemic hyperinsulinaemia. Chronic glucose infusion increased the plasma insulin response to acute hyperglycaemia more than twofold. These results demonstrate that chronic, physiologic hyperinsulinaemia, whether created by exogenous insulin infusion or by stimulation of endogenous insulin secretion, leads to the development of insulin resistance, which is characterized by a specific defect in the non-oxidative (glycogen synthetic) pathway. These findings indicate that hyperinsulinaemia should be considered, not only as a compensatory response to insulin resistance, but also as a self-perpetuating cause of the defect in insulin action.
Adult↗
Improvement of basal hepatic glucose production and fasting hyperglycemia of type I diabetic patients treated with human recombinant ultralente insulin.
OBJECTIVE: To test whether a suppertime injection of human ultralente insulin in patients with type I diabetes would result in a larger inhibition of basal hepatic glucose production (HGP) and improvement in fasting and mean daily plasma glucose levels. RESEARCH DESIGN AND METHODS: We studied 16 type I diabetic patients (41 +/- 4 years of age; body mass index [BMI] = 23.3 +/- 0.3 kg/m2; diabetes duration > 3 years) with a crossover protocol of therapy with an intermediate and ultralente insulin. All patients were already treated with three injections per day of regular insulin in addition to intermediate-acting (NPH) insulin at suppertime. After a 14-day run-in period, patients were randomly assigned to treatment with equivalent doses (10.8 +/- 0.8 U, at 1900) of intermediate (Humulin I) or ultralente (Humulin U) insulin. After 1 month of treatment, patients were crossed over. No change of the insulin dosage was performed during the study period. Basal HGP was measured by D-(6,6-2H2)-glucose infusion. Plasma glucose concentration was measured in the fasting state and monitored during the day. RESULTS: Before starting the study period, fasting plasma glucose was 13.4 +/- 1.1 mM and plasma free-insulin was 48.0 +/- 4.8 pM. Daily plasma glucose concentration averaged 10.3 +/- 0.3 mM and the area under the curve (AUC) was 1.41 +/- 0.05 mol/14 h. NPH insulin, given at suppertime for a month, did not induce significant changes in fasting plasma insulin (40.2 +/- 4.8 pM), glucose concentration (14.0 +/- 0.9 mM) or HGP (20.2 +/- 2.2 mumol.kg-1.min-1). Accordingly, no change occurred in the average daily plasma glucose (10.3 +/- 0.3 mM) or AUC (1.41 +/- 0.9 mol/14 h). Glycated hemoglobin also was not affected (8.2 +/- 0.4 vs. 8.2 +/- 0.3%). On the contrary, a 4-week treatment with ultralente insulin, also given at suppertime, was associated with a decline in the basal HGP (16.0 +/- 1.3 mumol.kg-1.min-1), fasting (11.3 +/- 0.9 mM) and average daily (9.4 +/- 0.3 mM) plasma glucose concentrations, and AUC (1.29 +/- 0.07 mol/14 h) of plasma glucose level (all P < 0.05). Glycated hemoglobin was reduced (7.9 +/- 0.4%). In each condition, fasting plasma glucose concentration was correlated with the average daily plasma glucose level (basal = 0.78; intermediate = 0.89; ultralente = 0.62; all P < 0.05), which suggests that ultralente insulin likely induces the improvements of metabolic control through reducing fasting plasma glucose. CONCLUSIONS: Our results suggest that treating type I diabetic patients with ultralente insulin at suppertime provides a better modulation of basal HGP so that lower fasting plasma glucose levels are ensured. The reduction of fasting hyperglycemia is likely to affect positively daily plasma glucose control.
Adult↗
Mechanism(s) of the blood glucose lowering action of benfluorex.
Benfluorex is a hypolipidaemic agent with biguanide-like properties. To evaluate its blood glucose lowering action, a single-blind study protocol was designed. Two groups of seven type II (non-insulin-dependent) diabetic patients matched for age (50 +/- 4 vs. 53 +/- 1 years), sex, body mass index (27.8 +/- 0.6 vs. 26.5 +/- 0.7 kg/m2), and duration of diabetes were studied before and after 1 month of treatment with benfluorex 150 mg tid (= tres in die = three times a day), PO (= per os = by mouth) or a placebo, respectively. All patients had previously been treated by diet alone. In all patients, parameters of glucose and lipid metabolism were obtained. Insulin sensitivity was assessed by means of a euglycaemic (5.1 +/- 0.1 mM) hyperinsulinaemic (516 +/- 28 pM) clamp performed in combination with [3(-3)H]glucose infusion and indirect calorimetry. In no case was there a significant change in body mass index (27.6 +/- 0.5 vs. 26.4 +/- 0.7 kg/m2). After 1 month of treatment, fasting plasma glucose (6.8 +/- 0.2 vs. 8.1 +/- 0.6 mM) and HbA1C (glycated haemoglobin; 6.5 +/- 0.2 vs. 8.0 +/- 0.7%) were lower in the benfluorex group than in the placebo-treated patients (both p < 0.05). No change was observed in hepatic glucose production (HGP) (13.5 +/- 1.4 vs. 13.9 +/- 1.1 mumol/min per kg), the basal rate of glucose, and lipid oxidation and non-oxidative glucose metabolism, or in plasma triglyceride and total cholesterol concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Appetite Depressants↗
Mechanisms of fasting hypoglycemia and concomitant insulin resistance in insulinoma patients.
To gain further insight into the pathogenesis of fasting hypoglycemia in patients with insulin-secreting adenoma of the pancreas, we studied seven patients affected by insulinoma (age, 42 +/- 7 years; body mass index [BMI], 27 +/- 2 kg/m2) and seven normal subjects. In insulinoma patients, hepatic glucose production (HGP) and glucose utilization (Rd) were evaluated by infusion of 3-3H-glucose at spontaneous fasting plasma glucose concentration, after restoration of euglycemia and during euglycemic insulin clamp (40 mU/m2/min). In insulinoma patients, fasting plasma glucose concentration (2.8 +/- 0.2 v 4.5 +/- 0.1 mmol/L; P < .001), HGP, and glucose Rd (7.8 +/- 1.1 v 12.0 +/- 0.3 mumol/kg/min; P < .01) were lower than in normal subjects, while plasma insulin level was higher (138 +/- 19 v 38 +/- 3 pmol/L; P < .001). In insulinoma patients after attainment of euglycemia (4.7 +/- 0.2 mmol/L) by exogenous glucose infusion, insulin level increased slightly (174 +/- 18 pmol/L; P < .01) and glucose Rd was similar to that of normal individuals (12.8 +/- 0.6 v 12.0 +/- 0.3 mumol/kg/min). During the clamp studies, glucose Rd was lower in insulinoma patients (18.7 +/- 1.2 v 33.8 +/- 3.1 mumol/kg/min; P < .01) despite higher plasma insulin concentration (612 +/- 48 v 420 +/- 12 pmol/L). Therefore, glucose Rd/I x 100 ratio (where I is plasma insulin concentration) was much lower in insulinoma patients (3.1 +/- 0.9 v 8.0 +/- 0.7; P < .01), suggesting a marked degree of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Body composition study in the elderly: comparison between tritium dilution method and dual photon absorptiometry.
BACKGROUND: The methods commonly employed in body composition study in elderly persons derive fat-free mass (FFM) by measures of total body water (TBW); these methods assume FFM hydration constant (TBW/FFM = 0.732). The aim of our study was to verify the accuracy of the TBW method in FFM estimation and to study the variability of fat-free mass hydration (TBW/FFM) in healthy elderly subjects. METHODS: We assessed FFM in 27 healthy old subjects (76 +/- 7 yrs) by dual photon absorptiometry (DPA) and by TBW measured by 3H2O. Furthermore, to verify the accuracy in FFM estimation by our methods, we measured resting metabolic rate (RMR) by indirect calorimetry. RESULTS: FFM hydration was 71.9 +/- 4.9 (range 63.6-80.4%), a range larger than that reported by direct chemical analysis in adults. The FFM hydration measured in our subjects was not different from the 73.2 value currently used in healthy adults. FFM values derived by TBW (assuming TBW/FFM = 0.732) were not significantly different from FFM measured by DPA. We correlated FFM with resting metabolic rate and found a similar correlation between RMR and FFM-DPA (r = .89, p < .001) and FFM-TBW (r = .85, p < .001). CONCLUSIONS: Both methods employed in our study have proved to be accurate in estimating FFM in elderly persons; particularly, the value of 0.732 assigned to FFM hydration to derive fat-free mass in adults can be employed also in body composition study of the elderly.
Absorptiometry, Photon↗
Characterization of cellular defects of insulin action in type 2 (non-insulin-dependent) diabetes mellitus.
Seven non-insulin-dependent diabetes mellitus (NIDDM) patients participated in three clamp studies performed with [3-3H]- and [U-14C]glucose and indirect calorimetry: study I, euglycemic (5.2 +/- 0.1 mM) insulin (269 +/- 39 pM) clamp; study II, hyperglycemic (14.9 +/- 1.2 mM) insulin (259 +/- 19 pM) clamp; study III, euglycemic (5.5 +/- 0.3 mM) hyperinsulinemic (1650 +/- 529 pM) clamp. Seven control subjects received a euglycemic (5.1 +/- 0.2 mM) insulin (258 +/- 24 pM) clamp. Glycolysis and glucose oxidation were quantitated from the rate of appearance of 3H2O and 14CO2; glycogen synthesis was calculated as the difference between body glucose disposal and glycolysis. In study I, glucose uptake was decreased by 54% in NIDDM vs. controls. Glycolysis, glycogen synthesis, and glucose oxidation were reduced in NIDDM patients (P < 0.05-0.001). Nonoxidative glycolysis and lipid oxidation were higher. In studies II and III, glucose uptake in NIDDM was equal to controls (40.7 +/- 2.1 and 40.7 +/- 1.7 mumol/min.kg fat-free mass, respectively). In study II, glycolysis, but not glucose oxidation, was normal (P < 0.01 vs. controls). Nonoxidative glycolysis remained higher (P < 0.05). Glycogen deposition increased (P < 0.05 vs. study I), and lipid oxidation remained higher (P < 0.01). In study III, hyperinsulinemia normalized glycogen formation, glycolysis, and lipid oxidation but did not normalize the elevated nonoxidative glycolysis or the decreased glucose oxidation. Lipid oxidation and glycolysis (r = -0.65; P < 0.01), and glucose oxidation (r = -0.75; P < 0.01) were inversely correlated. In conclusion, in NIDDM: (a) insulin resistance involves glycolysis, glycogen synthesis, and glucose oxidation; (b) hyperglycemia and hyperinsulinemia can normalize total body glucose uptake; (c) marked hyperinsulinemia normalizes glycogen synthesis and total flux through glycolysis, but does not restore a normal distribution between oxidation and nonoxidative glycolysis; (d) hyperglycemia cannot overcome the defects in glucose oxidation and nonoxidative glycolysis; (e) lipid oxidation is elevated and is suppressed only with hyperinsulinemia.
Adult↗
Transmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes.
Insulin resistance for glucose metabolism in skeletal muscle is a key feature in non-insulin-dependent diabetes mellitus (NIDDM). Which cellular effectors of glucose metabolism are involved is still unknown. We investigated whether transmembrane glucose transport in vivo is impaired in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in six nonobese NIDDM patients and five age- and weight-matched controls. Unlabeled D-mannitol (a nontransportable molecule) and radioactive 3-O-methyl-D-glucose (the reference molecular probe to assess glucose transport activity) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo transmembrane transport of 3-O-methyl-D-glucose in forearm muscle was determined by computerized analysis of the washout curves. At similar steady-state plasma concentrations of insulin (approximately 500 pmol/liter) and glucose (approximately 5.15 mmol/liter), transmembrane inward transport of 3-O-methyl-D-glucose in skeletal muscle was markedly reduced in the NIDDM patients (6.5 x 10(-2) +/- 0.56 x 10(-2).min-1) compared with controls (12.5 x 10(-2) +/- 1.5 x 10(-2).min-1, P < 0.005). Mean glucose uptake was also reduced in the diabetics both at the whole body level (9.25 +/- 1.84 vs. 28.3 +/- 2.44 mumol/min per kg, P < 0.02) and in the forearm tissues (5.84 +/- 1.51 vs. 37.5 +/- 7.95 mumol/min per kg, P < 0.02). When the latter rates were extrapolated to the whole body level, skeletal muscle accounted for approximately 80% of the defect in insulin action seen in NIDDM patients. We conclude that transmembrane glucose transport, when assessed in vivo in skeletal muscle, is insensitive to insulin in nonobese NIDDM patients, and plays a major role in determining whole body insulin resistance.
Adult↗
In vivo glucose metabolism in obese and type II diabetic subjects with or without hypertension.
This study examined whether the presence of hypertension, an insulin-resistant condition, exacerbates the defect in insulin action observed in obesity and type II diabetes mellitus. Glucose metabolism in the basal state and in response to insulin was quantitated by using the euglycemic insulin (20 mU.min-1 x m-2) clamp in combination with 3-[3H]glucose infusion and indirect calorimetry in 20 obese nondiabetic subjects (10 hypertensive and 10 normotensive), 26 type II diabetic subjects (13 hypertensive and 13 normotensive), and 11 normal nondiabetic subjects. The two groups of obese subjects and the two groups of diabetic subjects were matched for sex, age, race, body mass index, and fat distribution. Both in the basal state and during insulin infusion, glucose disposal rates (total, oxidative, and nonoxidative) were similar in obese subjects with or without hypertension. Compared with control subjects, both groups of obese subjects were markedly insulin resistant. Similarly, type II diabetic individuals, whether normotensive or hypertensive, were equally insulin resistant. The severity of insulin resistance was nearly identical in obese and diabetic groups. In diabetic subjects, the inhibitory effect of insulin on hepatic glucose output, lipolysis, and lipid oxidation was blunted compared with normal subjects. In obese subjects the ability of insulin to inhibit lipolysis and lipid oxidation was impaired. However, hypertension did not alter the suppressive effects of insulin on hepatic glucose production, plasma free fatty acid levels, or lipid oxidation in either obese or type II diabetic subjects. These results indicate that hypertension does not confer a greater severity of insulin resistance than that already is present in obesity and type II diabetes mellitus.
Adipose Tissue↗
Short-term effects of metformin on insulin sensitivity and sodium homeostasis in essential hypertensives.
Explore the source record for details and available documents.
Adult↗
[Hyperinsulinism. Causes and mechanisms].
A high plasma insulin concentration in the presence of a normal or high plasma glucose level appears to be a common feature of glucose intolerance, obesity, and hypertension. Hyperinsulinemia has been recognized as a major risk factor for the development of coronary artery disease independent of blood pressure and plasma lipid levels. All these conditions are frequently associated, particularly in aging, a state itself characterized by hyperinsulinemia. This common association has prompted the hypothesis that hyperinsulinemia may be a causative factor rather than the consequence of obesity, diabetes, hypertension, and hyperlipidemia. If that is the case, defining the nature and mechanisms of hyperinsulinemia becomes of primary interest. Insulin resistance is also a striking feature of all of the above mentioned pathologic states. In the presence of a preserved B-cell function, hyperinsulinemia can represent the mechanism designed to overcome the defect in the biological action of the hormone. For instance, there is a clear-cut age-related decline in the body's sensitivity to insulin. In order to compensate for this defect in insulin-mediated glucose metabolism, the B-cell must increase its secretion. On the other hand, a certain degree of insulin resistance can be induced both in animals and man by prolonged euglycemic hyperinsulinemia. Little is known regarding possible primary defects of the B-cell leading to uncontrolled oversecretion of insulin and subsequent insulin resistance. The primary defect, more probably, resides in an alteration of one or more of the steps whereby insulin exerts it own action. In favor of this hypothesis are the observations that insulin resistance segregates in familial clusters and that the first defect found in normoglycemic relatives of insulin-resistant diabetic patients is a reduced transformation of glucose into glycogen. Whatever is the primary defect, it is likely that a correction of insulin resistance might reduce the circulating levels of plasma insulin, possibly playing a beneficial effect on glucose tolerance, body weight, blood pressure and plasma lipid concentration.
Arteriosclerosis↗
[Mechanisms of hypoglycemic action of benfluorex].
UNLABELLED: Benfluorex is a hypolipidemic agent with biguanide-like properties. Its action on glucose metabolism was evaluated in 6 NIDDM patients previously treated with diet alone. Before and after 1 month of benfluorex therapy (450 mg/day p.o.), an euglycemic (100 mg/dl) insulin (40 mU/m2/min) clamp was performed along with 3-3H-glucose infusion and indirect calorimetry. Benfluorex did not affect body weight, while it reduced fasting plasma glucose (144 +/- 16 vs 119 +/- 8 mg/dl; P < 0.05), glycosylated hemoglobin (6.8 +/- 0.8 vs 6.4 +/- 0.4 percent) and fructosamine (2.9 +/- 0.6 vs 2.4 +/- 0.2 mmol/l; P < 0.05). Both triglycerides (2.3 +/- 0.6 vs 1.9 +/- 0.5 mmol/l) and total cholesterol (5.7 +/- 0.7 vs 5.2 +/- 0.6 mmol/l) declined. No changes occurred in plasma fatty acid, insulin, and C-peptide. Basal hepatic glucose production did not change and it was completely suppressed during the clamp studies both before and after benfluorex. Basal oxidation rates of carbohydrates and lipids did not change significantly. During the insulin clamp study, insulin-mediated glucose disposal increased after benfluorex (5.7 +/- 0.3 vs 4.8 +/- 0.2 mg/kg/min; P < 0.01). Lipid oxidation was equally suppressed before and after therapy with benfluorex. Glucose oxidation was not enhanced after benfluorex while non-oxidative glucose metabolism was significantly improved (2.2 +/- 0.7 vs 3.4 +/- 0.4 mg/kg/min; P < 0.05). CONCLUSION: short-term benfluorex administration a) improves glucose and lipid control, b) improves insulin action by enhancing non-oxidative glucose metabolism, c) does not affect basal insulin secretion. The long-term effect of benfluorex treatment remains to be evaluated.
Blood Glucose↗
The contribution of hyperglycaemia and hypoinsulinaemia to the insulin resistance of streptozotocin-diabetic rats.
The relative contribution of hyperglycaemia and hypoinsulinaemia was evaluated in rats made diabetic by streptozotocin administration. Four groups of rats were studied: untreated normal rats; streptozotocin-diabetic; streptozotocin-diabetic treated with phlorizin (0.4 mg/kg body weight per day); streptozotocin-diabetic mildly treated with insulin (0.7 IU/day). In all groups, insulin action (responsiveness) was assessed with the euglycaemic (5.3 mmol/l) hyperinsulinaemic (524 mU/l) clamp technique combined with 3H-2-deoxy-D-glucose method, enabling determination of the glucose utilization index in various tissues. Responsiveness of the overall glucose utilization process to insulin was reduced by 28% in streptozotocin-diabetic rats (12.0 +/- 1.2 vs 16.5 +/- 0.6 mg.kg-1.min-1, p less than 0.001). This was associated with a significant reduction (p less than 0.05) in the glucose utilization index in all muscles studied (average = 17.0 vs 32.1 ng.mg of tissue-1.min-1), in the heart (19.6 vs 39.5 ng.mg-1.min-1), brown adipose tissue (98.9 vs 178.0 ng.mg-1.min-1), skin (6.4 vs 13.1 ng.mg-1.min-1). Phlorizin treatment normalized plasma glucose levels without affecting those of insulin, and restored overall glucose utilization to normal (16.6 +/- 1.0 mg.kg-1.min-1). This normalization was accompanied by a normalization of the glucose utilization index in all muscle types studied (29.2 ng.mg-1.min-1), in the heart (50.0 ng.mg-1.min-1), brown adipose tissue (157.2 ng.mg-1.min-1), and skin (10.0 ng.mg-1.min-1). White adipose tissue, brain and gut were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Retrospective analysis of daily glucose profile in type 1 diabetic patients with continuous subcutaneous insulin infusion (CSII).
A retrospective analysis of blood glucose control was performed in 17 type 1 diabetic patients who regularly monitored their blood glucose concentration by visual strips over a period of 3-83 months. Analysis was performed by a patient management software loaded on a personal computer. In this cohort of patients the average daily blood glucose reading was 1.6 +/- 0.3. Blood glucose readings were collected more frequently following meal ingestion (40.3%) than in the post-absorptive state (24.6%; P less than 0.05). Blood glucose concentration fluctuated from a basal level of 146 +/- 5 mg/dl to 167 +/- 4 mg/dl in the post-prandial phases with an average daily value of 156 +/- 2 mg/dl. Blood glucose values below 80 mg/dl were evenly distributed throughout the day, while hyperglycemia (greater than 300 mg/dl) occurred more commonly after meals (42%). Daily blood glucose was higher during weekends (164 +/- 5 mg/dl) than during weekdays (155 +/- 2 mg/dl; P less than 0.05). A weak correlation was found between the number of blood glucose readings/day and daily blood glucose level. These results suggest that long-term maintenance of satisfactory metabolic control is attainable in type 1 diabetic patients and that this is mainly dependent upon subject self awareness.
Adult↗
Ketone body metabolism in NIDDM. Effect of sulfonylurea treatment.
We assessed the metabolism of the two KBs, AcAc and 3-BOH; the relationships between ketogenesis and FFA inflow rate; and the effect of chronic sulfonylurea treatment in mild NIDDM patients (plasma glucose less than 10 mM). We studied 10 nonobese NIDDM patients in a crossover, randomized, double-blind, placebo-controlled fashion. Each patient was studied 4 times: after a run-in period with placebo, after 3 mo of placebo treatment, after 3 mo of glibenclamide treatments, respectively, and after 3 mo of sulfonylurea treatment during an acute exogenous Intralipid infusion. Ten normal, nondiabetic subjects served as the control group. Glibenclamide treatment decreased plasma FFAs. When these substrates were exogenously increased, plasma FFAs were comparable with placebo and baseline concentrations. In NIDDM patients, baseline and placebo blood total KB concentration was significantly higher than in control subjects (216 +/- 22 and 244 +/- 25, respectively vs. 127 +/- 18 microM; P less than 0.01). Glibenclamide treatment significantly decreased total KBs to 177 +/- 19 microM (P less than 0.05). When FFAs were exogenously increased, total KBs were similar to the placebo and baseline period. In the baseline study, the AcAc/3-BOH ratio was 0.72 +/- 0.06 in control subjects, whereas in NIDDM patients, the ratio was 1.61 +/- 0.13 at baseline (P less than 0.001 vs. control subjects), 1.66 +/- 0.15 during placebo, 1.57 +/- 0.09 during glibenclamide (NS vs. baseline), and 1.51 +/- 0.23 during glibenclamide plus placebo FFAs. Both the AcAc interconversion rate to 3-BOH and the 3-BOH interconversion rate to AcAc were significantly lower in NIDDM patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Total body fat content and fat topography are associated differently with in vivo glucose metabolism in nonobese and obese nondiabetic women.
In this study, total body fat content and fat topography were related to glucose metabolism in the basal and insulin-stimulated states in 18 nonobese and 18 obese premenopausal nondiabetic women. All subjects received a euglycemic insulin (20 mU.min-1.m2) clamp study in combination with [3-3H]-D-glucose infusion and indirect calorimetry to quantitate total body glucose uptake, glucose oxidation, and nonoxidative glucose disposal. Total body fat content was determined with tritiated water, whereas body fat distribution was estimated from the WHR, the STR, and the VSR (measured by magnetic resonance imaging). In the postabsorptive state, total body glucose utilization, glucose oxidation, and nonoxidative glucose disposal rates were similar in nonobese and obese women, whereas during the insulin clamp all three metabolic parameters were reduced significantly in the obese group. In nonobese women, total body fat content was related inversely to both total and nonoxidative glucose disposal during the insulin clamp, whereas no relationship was found between glucose metabolism (total, oxidative, and nonoxidative) and WHR, STR, or VSR. In contrast, in obese women, no relationship was observed between total body fat content and any measure of insulin-mediated glucose metabolism. However, both WHR and VSR were related inversely to total, oxidative, and nonoxidative glucose disposal rates during the insulin clamp. These results suggest that total body fat content and body fat topography are associated differently with insulin-mediated glucose metabolism in nonobese and obese women. In the nonobese women, total body fat mass appears to be a primary determinant of tissue sensitivity to insulin, whereas in obese women, body fat topography exerts a more dominant effect.
Adipose Tissue↗
Hepatic sensitivity to insulin: effects of sulfonylurea drugs.
Insulin regulation of hepatic glucose production (HGP) is altered in non-insulin-dependent diabetes mellitus (NIDDM), resulting in increased glucose output by the liver; this contributes to the elevation in plasma glucose concentration observed both in the basal state and postprandially. Therefore, restoration of normal insulin action in the liver must be a goal of hypoglycemic therapy. Sulfonylureas have been widely used for treatment of NIDDM over the past 30 years. In addition to their stimulatory effect on insulin secretion, these compounds seem to possess extrapancreatic effects. Early in vitro studies showed that addition of sulfonylureas to the perfusion medium of liver preparations could exert a significant suppressive effect on HGP. Subsequent experience suggested that these compounds could act at the level of the insulin receptor as well as at various postreceptor sites. These studies showed that sulfonylureas may inhibit glycogenolysis and gluconeogenesis while stimulating glycogen synthesis. Results obtained in vivo in NIDDM patients are in agreement with the in vitro studies. Long-term treatment with sulfonylureas is associated with a decline in fasting plasma glucose concentration and a parallel reduction in HGP. Nevertheless, the direct effect of sulfonylurea administration on the liver remains unclear, since the reduction in HGP that occurs during sulfonylurea treatment may be secondary to an overall improvement in insulin secretion. It is also of interest that in insulin-dependent diabetic patients, sulfonylurea administration in combination with insulin injections is not followed by a significant change in HGP. Possible effects of sulfonylureas on glucagon secretion and on the metabolism of free fatty acids (FFAs) may also contribute to improved sensitivity of the liver to the suppressive action of insulin, since these agents appear to reduce plasma glucagon and FFA concentrations. Thus, present data support an extrapancreatic action of sulfonylureas on the liver. However, it does appear that a certain degree of residual insulin secretion is required for sulfonylurea agents to elicit their hepatic effect.
Animals↗