Insulin sensitivity is not impaired in Mexican-American women without a family history of diabetes.

Objective: The purpose of this research was to compare insulin sensitivity in Mexican-Americans and non-Hispanic whites without a family history of diabetes to establish whether insulin resistance is a defect intrinsically related to subjects of Mexican origin.

Research Design And Methods: In study A, we compared insulin sensitivity in 12 Mexican-American and 12 non-Hispanic white women with normal glucose tolerance and no family history of diabetes. In study B, we compared insulin sensitivity in two groups of normal glucose-tolerant Mexican-Americans, nine with a positive (FHD+) and nine with a negative (FHD-) family history of diabetes.

Bedtime insulin/daytime glipizide. Effective therapy for sulfonylurea failures in NIDDM.

Bedtime insulin (BI)/daytime sulfonylurea (DSU) therapy was studied double-blind in 30 non-insulin-dependent diabetes mellitus subjects in whom sulfonylurea (SU) therapy had failed. Subjects were switched to glipizide for 2 months (phase I) to confirm failure (fasting plasma glucose [FPG] 12.0 +/- 0.

Acute effect of human recombinant insulin-like growth factor I on renal function in humans.

We examined the acute effects of insulin-like growth factor I (IGF-I) on renal function in 8 normal subjects who received a 3-hour intravenous infusion of IGF-I at a rate of 0.4 micrograms/kg.min.

Effect of amino acid infusion on renal hemodynamics in humans: a dose-response study.

We evaluated the dose-response relationship between the plasma amino acid (AA) concentration and renal hemodynamics in eight normal subjects. After an overnight fast, a balanced 10% AA solution was infused for 180 min at five separate infusion rates: 0.5 (group I), 1.

Glucose absorption and production following oral glucose: comparison of compartmental and arteriovenous-difference methods.

Both whole-body models and the regional arteriovenous (AV)-difference method have been used to calculate systemic glucose rates of appearance (Ras) under non-steady-state conditions. Although whole-body models have been experimentally validated in the dog, direct comparison of the whole-body and regional-balance approach has not been made in man. We reanalyzed published data obtained by combining the double-tracer technique ([3H]glucose infusion with ingestion of a [14C]glucose-labeled load) with hepatic vein catheterization.

The Diabetes Control and Complications Trial Study: implications for the diabetic foot.

The pathogenesis of foot problems in patients with diabetes mellitus involves multiple factors including macrovascular disease, microvascular disease, abnormalities in blood flow distribution, peripheral neuropathy, autonomic neuropathy, physical stress, and infection. Surprisingly, the role of poor glycemic control in the development of diabetic foot complications has not been well studied. Recently, the Diabetes Control and Complications Trial has provided conclusive evidence that hyperglycemia plays a major role in the development of microvascular complications.

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.

Diabetic nephropathy: pathogenetic basis for treatment.

For maximal effectiveness, interventions to prevent diabetic nephropathy are initiated prior to clinically detectable proteinuria--during the microalbuminuria stage. Effects of therapy in relation to pathologic processes are described.

Time-dependent regulation by insulin of leucine metabolism in young healthy adults.

The long- and short-term effects of insulin on leucine turnover were investigated in six young healthy volunteers using [1-14C]leucine in combination with indirect calorimetry. After baseline measurement of leucine turnover (44.9 +/- 2.

Free fatty acid and glucose metabolism in human aging: evidence for operation of the Randle cycle.

We assessed insulin effects on plasma free fatty acid (FFA) and glucose metabolism in seven elderly (71 +/- 2 yr) and in seven younger (21 +/- 1 yr) subjects matched for body weight and body mass index but not for percent body fat (32.4 +/- 3.8% in elderly vs.

Glycogen turnover during refeeding in the postabsorptive dog: implications for the estimation of glycogen formation using tracer methods.

Recent 13C nuclear magnetic resonance (13C-NMR) studies in the anesthetized rat and perfused liver suggest that hepatic glycogen is simultaneously synthesized and degraded, even during combined hyperglycemia and hyperinsulinemia. The presence of glycogen turnover would confound efforts to study glycogen repletion with the use of tracer methods during feeding, particularly if the liver is not glycogen-depleted. To ascertain whether glycogen turnover occurs during normal feeding, we measured liver uptake of glucose in 10 awake, healthy, postabsorptive dogs with long-term arterial, portal, and hepatic venous catheters before and for 3 hours after a meal of either glucose alone (1.

Effects of physiological hyperinsulinemia on the intracellular metabolic partition of plasma glucose.

Methodology for assessing the glycolytic and oxidative fluxes from plasma glucose, by measuring 3H2O and 14CO2 rates of production during [3-3H]- and [U-14C]glucose infusion, was tested in healthy subjects. In study 1, during staircase 3H2O infusion in six subjects, calculated rates of 3H2O appearance agreed closely with 3H2O infusion rates. In study 2, when [2-3H]glucose and NaH14CO3 were infused in four subjects in the basal state and during a 4-h euglycemic insulin (approximately 70 microU/ml) clamp, accurate estimates of the rates of [2-3H]glucose detritiation were obtained (94-97% of the expected values), and the recovery factor of NaH14CO3 did not change during hyperinsulinemia.

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.

Glucose metabolism during the menstrual cycle. Assessment with the euglycemic, hyperinsulinemic clamp.

To assess tissue sensitivity to insulin during the follicular and luteal phases of the menstrual cycle, two-step euglycemic, hyperinsulinemic clamp studies in combination with tritiated glucose infusion and indirect calorimetry were performed in regularly menstruating women in randomized order. There was no difference in the basal follicular and luteal phase levels of glucose, insulin or glucose turnover. A low-dose (0.

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.

Contribution of muscle and liver to glucose-fatty acid cycle in humans.

To examine the influence of elevated free fatty acid (FFA) levels on hepatic glucose production (HGP) and oxidative and nonoxidative pathways of glucose metabolism, 12 healthy subjects participated in two euglycemic insulin-clamp studies performed with and without infusion of Intralipid plus heparin. To elucidate the role of skeletal muscle in this putative interaction, we performed muscle biopsies for the measurement of activities of glycogen synthase (GS), pyruvate dehydrogenase (PDH), and carnitine palmitoyltransferase (CPT). Infusion of Intralipid plus heparin caused an increase in plasma FFA concentrations and rate of lipid oxidation (measured by indirect calorimetry) that was not inhibited by insulin.

Effect of insulin on system A amino acid transport in human skeletal muscle.

Transmembrane transport of neutral amino acids in skeletal muscle is mediated by at least four different systems (system A, ASC, L, and Nm), and may be an important target for insulin's effects on amino acid and protein metabolism. We have measured net amino acid exchanges and fractional rates of inward (k(in), min-1) and outward (kout, min-1) transmembrane transport of 2-methylaminoisobutyric acid (MeAIB, a nonmetabolizable amino acid analogue, specific for system A amino acid transport) in forearm deep tissues (skeletal muscle), by combining the forearm perfusion technique and a novel dual tracer ([1-H3]-D-mannitol and 2-[1-14C]-methylaminoisobutyric acid) approach for measuring in vivo the activity of system A amino acid transport. Seven healthy lean subjects were studied.

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.

Glucose transport in human skeletal muscle. The in vivo response to insulin.

Transmembrane glucose transport plays a key role in determining insulin sensitivity. We have measured in vivo WBGU, FGU, and K(in) and K(out) of 3-O-methyl-D-glucose in forearm skeletal muscle by combining the euglycemic clamp technique, the forearm-balance technique, and a novel dual-tracer (1-[3H]-L-glucose and 3-O-[14C]-methyl-D-glucose) technique for measuring in vivo transmembrane transport. Twenty-seven healthy, lean subjects were studied.

Influence of basal androgen levels in euandrogenic women on glucose homeostasis.

Objective: To evaluate possible relationships between insulin action and the normal variations of serum androgens in euandrogenic women.

Design: Prospective evaluation of insulin action in normal nonobese women using hyperglycemic and euglycemic hyperinsulinemic clamp techniques, correlating insulin action to serum testosterone (T), free T, androstenedione (A), and dehydroepiandrosterone sulfate (DHEAS). Statistical analysis used Spearman's rank correlation.

The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents.

NIDDM patients with overt fasting hyperglycemia are characterized by multiple defects involving both insulin secretion and insulin action. At this point of the natural history of NIDDM, however, it is difficult to establish which defects are primary and which are acquired secondary to insulinopenia and chronic hyperglycemia. To address this question, we have studied the glucose-tolerant offspring (probands) of two Mexican-American NIDDM parents.

Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity.

The dose-response relationship between the plasma insulin concentration and oxidative and nonoxidative pathways of free fatty acid (FFA) metabolism was examined in 11 obese and 7 lean subjects using a stepwise insulin clamp technique in combination with indirect calorimetry and infusion of [1-14C]palmitate. The fasting plasma FFA concentration was elevated in obese subjects (793 +/- 43 vs. 642 +/- 39 mumol/l; P less than 0.

Pathogenesis of NIDDM. A balanced overview.

Non-insulin-dependent diabetes mellitus (NIDDM) results from an imbalance between insulin sensitivity and insulin secretion. Both longitudinal and cross-sectional studies have demonstrated that the earliest detectable abnormality in NIDDM is an impairment in the body's ability to respond to insulin. Because the pancreas is able to appropriately augment its secretion of insulin to offset the insulin resistance, glucose tolerance remains normal.