Search PubMed⌕ Search

Biomedical subjects

H E Lebovitz

Publications and source records attributed to H E Lebovitz.

At least 19 recordsLinked to original sources
PubMed1996

Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis.

Chronic pancreatitis (CP) is associated with lowered plasma levels and a blunted nutrient-induced release of pancreatic polypeptide (PP). To investigate the possible role of PP on glucose metabolism, we studied male patients with documented CP (n = 5) and obesity-matched control subjects (NL) (n = 6). Hepatic glucose production (HGP) and overall glucose disposal rates were determined by [3-3H]glucose infusion during a hyperinsulinemic-euglycemic clamp during three separate admissions. Basal rates of HGP were higher in CP patients. In response to an infusion of insulin (60 pmol.m-2.min-1), HGP fell 91 +/- 5% in NL subjects but only 68 +/- 8% in CP subjects (P < 0.05). One month later, the clamp was repeated during the final 2 h of an 8-h infusion of bovine PP (2 pmol.kg-1.min-1). HGP before the insulin infusion and its subsequent suppression (NL: 83 +/- 5%; CP: 86 +/- 15%) were nearly identical between groups. In follow-up studies 1 month after the PP infusion, HGP both basally and in response to insulin alone were similar to the first study. During oral glucose tolerance tests (OGTT) performed 18 h after the PP infusion, subjects with normal (n = 7) baseline OGTT responses showed no effect. All patients with diabetic (n = 3) or nondiagnostic (n = 1) OGTT responses, however, demonstrated lowered mean plasma glucose levels (approximately -2.3 mmol/L; range: -0.6 to -7.2 mmol/L). OGTTs repeated 1 month after the PP treatment showed a return to pretreatment responses. We conclude that chronic pancreatitis accompanied by PP deficiency is associated with partial hepatic resistance both in the basal state and in response to hyperinsulinemia. This impairment is reversed after iv PP administration. PP deficiency may therefore play a role in the development of pancreatogenic diabetes caused by pancreatic injury.

Adult↗
PubMed1996

Long-term normoglycemic remission in black newly diagnosed NIDDM subjects.

We have defined and characterized the natural history of spontaneous near-normoglycemic remission off of antidiabetic medication in 79 black NIDDM subjects. They had initially presented with plasma glucose levels of 37.8 +/- 19.3 mmol/l. Baseline clinical metabolic and 8-year prospective data were obtained (51 men and 28 women, mean age 45 +/- 10 years, islet-cell or GAD antibody negative). After hospitalization and intensive outpatient treatment, near-normoglycemic remission (fasting plasma glucose 6.1 +/- 0.83 mmol/l and HbA1c 0.95 +/- 0.10 of upper limit of normal) occurred within 8 +/- 10 months of insulin or sulfonylurea therapy. This was unrelated to the resolution of stress or significant weight loss (1.9 +/- 4.97 kg). Metabolic studies performed during remission showed 17% normal, 33% impaired, and 50% diabetic glucose tolerance. Glucose disposal (1 mU x kg-1 x min-1) euglycemic insulin clamp with D-[3(-3)H]glucose) was higher in the normal glucose tolerance group compared with the impaired and diabetic groups (37.8 +/- 10.2 vs. 26.1 +/- 10.7 and 26.7 +/- 12.0 micromol x kg-1 x min-1; P < 0.05) despite similar BMIs in all three groups (28.8 +/- 3.7 kg/m2). Insulin secretion was below the normal range. Of 79 patients, 27 relapsed. A Kaplan-Meier survival analysis gives a median time of 40 months to relapse. Higher presenting plasma glucose and male sex predicted earlier relapse. Near-normoglycemic remission may occur in up to 30% of black new-onset NIDDM patients. It appears to be associated with intensive initial glycemic regulation and may be a method of decreasing the development of microvascular complications in NIDDM.

Adult↗
PubMed1995

Metabolic effects of darglitazone, an insulin sensitizer, in NIDDM subjects.

Insulin resistance is a significant pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM). A new class of drugs, the thiazolidinediones, have been shown to lower blood glucose levels without stimulating insulin secretion. We report the metabolic effect of the thiazolidinedione, darglitazone, in obese NIDDM subjects. Nineteen subjects were enrolled in a double-blind placebo-controlled study in which 25 mg of darglitazone was given once a day for 14 days. Nine subjects received the active drug and ten subjects received placebo. Darglitazone-treated subjects showed; 1) a decrease in 24-h plasma glucose area under the curve from 292.8 +/- 31.2 to 235.2 +/- 21.6 mmol.h-1.l-1 p = 0.002; 2) a decrease in 24-h serum insulin area under the curve from 1027.2 +/- 254.4 to 765.6 +/- 170.4 microU.h-1.l-1 p = 0.045; 3) a decrease in 24-h non-esterified fatty acid area under the curve from 1900 +/- 236 to 947 +/- 63 g.h-1.l-1 p = 0.002; 4) a decrease in mean 24-h serum triglyceride by 25.9 +/- 6.2% as compared to -3.9 +/- 4.8% for the placebo-treated group, p = 0.012. Placebo-treated subjects showed no change in their metabolic parameters after treatment. Thus, darglitazone is effective in increasing insulin effectiveness in obese NIDDM subjects. The potential for this and similar drugs to treat or prevent NIDDM as well as the insulin-resistance syndrome needs to be explored.

Blood Glucose↗
PubMed1995

Interaction of hypertension and diabetes on renal function in black NIDDM subjects.

We studied renal function of 194 black subjects with duration of diagnosed NIDDM from 1 month to 36 years to determine the interaction of hypertension and diabetes on nephropathy. Renal function was assessed by isotopic GFR and RPF studies, and serum creatinine. One hundred seventeen of the 194 subjects had 24-hour urinary albumin excretion (AER). AER > 300 mg/24 h correlated with longer duration of NIDDM, decrease in GFR and RPF, and rise in serum Cr, and all subjects were hypertensive. AER 30 to 300 mg/24 h also correlated with a longer duration of NIDDM and 80% had hypertension. When 194 subjects were grouped according to duration of NIDDM and the presence or absence of hypertension, subjects who remained normotensive had normal renal function. In hypertensive subjects a decrease in GFR occurred with duration of NIDDM > 1 year and decrease in RPF with duration of NIDDM > 5 years. In hypertensive subjects with NIDDM > 10 years, 36% had impaired renal function (GFR < 80 ml/min/1.73 m2 or serum creatinine > 1.4 mg/dl) and 75% had microalbuminuria or clinical proteinuria. Within this group, those subjects who developed hypertension after their diagnosis of diabetes were likely to have evidence of nephropathy as compared to those subjects whose hypertension was diagnosed prior to or simultaneous with their diabetes: 17 of 20 (85%) versus 7 of 13 (54%), respectively (P = 0.05). These data provide insight into the relationship between hypertension and diabetes in the development of nephropathy in black NIDDM individuals.

Adolescent↗
PubMed1995

Does intra-abdominal adipose tissue in black men determine whether NIDDM is insulin-resistant or insulin-sensitive?

Insulin resistance in black Americans with non-insulin-dependent diabetes mellitus (NIDDM) is found in only 60% of those with a body mass index (BMI) of < 30 kg/m2, suggesting that NIDDM can occur independent of peripheral insulin resistance. When insulin resistance is present, it is not necessarily correlated with obesity. Numerous studies have shown that increased amounts of intra-abdominal adipose tissue are associated with various metabolic abnormalities. We therefore investigated whether the occurrence of insulin resistance in black NIDDM men could be explained by the pattern of body adipose tissue distribution rather than total adiposity. Twenty-two near-normoglycemic black men (fasting plasma glucose [mean +/- SD] = 104 +/- 10 mg/dl, HbA1c = 4.6 +/- 0.78%, age 48.9 +/- 9.2 years, and BMI 26.5 +/- 2.4 kg/m2) were studied. The euglycemic insulin clamp with 1 mU.kg-1.min-1 insulin infusion and D-[3-3H]glucose was used to measure insulin action. Whole-body computed tomography with 22 scans was used to determine body composition. Total body adipose tissue was 19.6 +/- 7.51, and the percentage of body fat was 27 +/- 7. Glucose disposal ranged from 2.5 to 8.1 mg.kg-1.min-1 (10 men were insulin-sensitive and 12 were insulin-resistant). There was a strong inverse correlation between glucose disposal and the proportion of total adipose tissue in the intra-abdominal region (r = -0.78, P < 0.001), while there was no correlation between glucose disposal and total muscle volume, BMI, total adipose tissue volume, or total subcutaneous adipose tissue volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1995

Prolongation of near-normoglycemic remission in black NIDDM subjects with chronic low-dose sulfonylurea treatment.

Microvascular and neuropathic complications of diabetes mellitus can be significantly decreased by long-term, near-normoglycemic regulation in patients with insulin-dependent diabetes mellitus. Prevention or delay of onset of hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) patients should reduce morbidity and mortality from these complications. NIDDM can be nearly normoglycemic when diagnosed by screening before its symptomatic stage or when clinically hyperglycemic NIDDM goes into remission. One potential strategy to delay the onset of hyperglycemia in individuals at high risk is chronic low-dose sulfonylurea therapy. Thirty black NIDDM subjects who recently had developed near-normoglycemia were followed with no treatment or were randomly assigned to a 3-year, double-blind glipizide or placebo treatment. Baseline and follow-up parameters included fasting plasma glucose (FPG), HbA1c, plasma insulin, and glucose responses to an oral glucose tolerance test and insulin action, as determined by the euglycemic insulin clamp. Baseline FPG and HbA1c for all three groups were 107 mg/dl and 4.7%, respectively. Relapse to hyperglycemia was defined as an FPG level > or = 140 mg/dl on several consecutive visits or an FPG level > or = 140 mg/dl and symptoms of hyperglycemia. During the course of the treatment and follow-up, hyperglycemia occurred in 6 of 10 subjects in the no treatment group, 6 of 10 in the placebo group, and 2 of 10 in the glipizide treatment group. Prolongation of near-normoglycemia was significantly (P < 0.05) increased by low-dose (2.5 mg/day) glipizide compared with placebo treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗
PubMed1995

Liver fat, serum triglycerides and visceral adipose tissue in insulin-sensitive and insulin-resistant black men with NIDDM.

OBJECTIVE: We investigated the relationship of liver fat to visceral adipose tissue, serum triglyceride levels and glucose disposal. DESIGN: Cross-sectional, prospective. SUBJECTS: 21 lean to moderately obese black NIDDM men (mean +/- s.d. age 48.9 +/- 9.4 years, body mass index 26.3 +/- 2.4, fasting plasma glucose 104 +/- 10 mg/dl, HBA1C 4.6 +/- 0.8% and body fat 26 +/- 6%) with no evidence of liver disease or alcohol abuse. Eleven were insulin-sensitive (glucose disposal > 5.5 mg/kg/min) and ten were insulin-resistant subjects during euglycemic insulin clamps. MEASUREMENTS: Body composition and liver density were determined by whole body computed tomography using 22 scans. Liver fat score was defined as 100 minus the absolute liver density. Glucose disposal was measured during 1 mU/kg/min euglycemic insulin clamp with 3-3H glucose. RESULTS: Visceral adipose tissue volume was 3.54 +/- 1.87 litres. The liver fat score was 48.8 +/- 5.0 (not in the range of clinical hepatic steatosis). Glucose disposal ranged from 2.5 to 8.1 mg/kg/min. The liver fat score was correlated with visceral/total adipose tissue ratio (r = 0.65, P = 0.001) and to fasting serum triglyceride levels (r = 0.47, P = 0.032). Fasting serum triglyceride levels were related to visceral adipose tissue (r = 0.52, P = 0.016). Liver fat was inversely related to glucose disposal (r = -0.42, 1 tail P = 0.036). CONCLUSIONS: In non-insulin-dependent diabetes mellitus, liver fat may contribute to insulin resistance and be a link between visceral adipose tissue mass and serum triglyceride levels.

Adipose Tissue↗
PubMed1994

GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. Flatbush diabetes.

The objective of this study is to understand the metabolic and immunologic basis of diabetes in adult blacks with diabetic ketoacidosis (DKA). Twenty-one black adults presenting with DKA ([mean +/- SD] blood pH = 7.18 +/- 0.09, plasma glucose = 693 +/- 208 mg/dl, and positive serum ketones) had a subsequent clinical course of non-insulin-dependent diabetes mellitus (NIDDM). Human leukocyte antigens (HLAs) DR and DQ and antibodies to glutamic acid decarboxylase (GAD) and islet cell cytoplasmic proteins (ICP) were measured to assess autoimmunity. Insulin action was evaluated by the euglycemic insulin clamp, and insulin secretion was measured by C-peptide responses to oral glucose. Ketoacidosis was treated with insulin. Two subjects had a precipitating illness; four had a history of NIDDM. At the time of study, subjects' glycemic control was good (HbA1c = 5.7 +/- 1.6%). Nine subjects were treated with insulin, and 12 were on either sulfonylurea treatment or diet alone. Men (n = 12) were younger than women (n = 9) (40.8 +/- 9.8 and 51.1 +/- 6.3 years of age, respectively, P < 0.05) but similar in body mass index (27.8 +/- 2.7 and 29.98 +/- 4.1 kg/m2, respectively). Antibodies to GAD and ICP were absent. All but one subject was insulin resistant compared with normal subjects (glucose disposal 3.56 +/- 0.04 vs. 6.86 +/- 0.02 mg.kg-1.min-1), and insulin secretion was lower. HLA DR3 and DR4 frequency was higher than in nondiabetic black control subjects (65 vs. 30%, P < 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Empty sella.

Explore the source record for details and available documents.

Adult↗
PubMed1994

Renal protective effects of enalapril in hypertensive NIDDM: role of baseline albuminuria.

The primary results of a three-year prospective, double-blind, placebo-controlled trial in non-insulin-dependent diabetic (NIDDM) patients show that an anti-hypertensive regimen, which includes the ACE inhibitor enalapril, preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors (J Am Soc Nephrol 3:335, 1992). The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis. Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [baseline glomerular filtration rate (GFR) 30 to 100 ml/min/1.73 m2]. Twenty-four hour urinary excretion of albumin (UAE), protein, urea nitrogen, creatinine and isotopically determined GFR were measured at baseline and six month intervals. Glycemic control and blood pressure regulation were assessed every three months. The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline (UAE > 300 mg/24 hr) as compared to patients with baseline sub-clinical proteinuria (UAE < or = 300 mg/24 hr). Antihypertensive treatment with enalapril preserved GFR significantly better (P < 0.01) in the patients with sub-clinical proteinuria at baseline (UAE < or = 300 mg/24 hr) than other antihypertensive treatments which excluded the ACE inhibitor. Furthermore, only 7% of the enalapril-treated group progressed to clinical albuminuria compared to 21% of control treated patients. Although the enalapril-treated group had a lower mean blood pressure during the maintenance period, no correlation between blood pressure (systolic, diastolic or mean arterial) and rate of change of GFR was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Do blacks with NIDDM have an insulin-resistance syndrome?

NIDDM has been postulated to be a component of a more generalized metabolic syndrome, Syndrome X, caused by insulin resistance. Although the components of the syndrome include glucose intolerance, hypertension, increased TG, and decreased HDL cholesterol, their relationship to insulin resistance and/or hyperinsulinemia is controversial. Recent investigations have shown racial differences in the relationship between insulin resistance and BP in nondiabetic populations. We assessed the relationship between insulin resistance and the other components of the syndrome in 37 black men and 53 black women with NIDDM. Insulin sensitivity was determined by measuring glucose disposal with the euglycemic insulin clamp technique with a 1 mU.kg-1.min-1 insulin infusion. We also determined fasting lipid profiles and BP. In this group of black men and women with NIDDM, 30% were insulin sensitive, and 70% were insulin resistant. No correlation existed between insulin sensitivity and sBP or dBP in either sex. Fasting serum TGs were inversely correlated with insulin sensitivity for both men (r = -0.401, P = 0.02) and women (r = -0.366, P = 0.008). Serum HDL cholesterol was highly correlated with insulin sensitivity for men (r = 0.421, P = 0.01) but not for women (r = 0.071, P = 0.62). Fasting serum TG levels and serum HDL-cholesterol levels were highly correlated in an inverse relationship in men (r = -0.368, P = 0.03), but not women (r = -0.199, P = 0.17). In summary, BP does not correlate with insulin resistance in blacks with NIDDM. Normal insulin sensitivity occurs in 33% of black men and 25% of black women with NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

HLA-DQ associations distinguish insulin-resistant and insulin-sensitive variants of NIDDM in black Americans.

OBJECTIVE: NIDDM in black Americans exists as two variants: one with a primary defect in insulin action (insulin-resistant variant) and the other with normal insulin action and a primary defect in insulin secretion (insulin-sensitive variant). The objective of this study was to determine whether these two variants were genetically distinct from each other and from normal control subjects as determined by HLA typing. RESEARCH DESIGN AND METHODS: Insulin action was measured with the euglycemic insulin clamp with a 1 mU.kg-1.min-1 insulin infusion with [3-3H]glucose. A glucose disposal of < 278 mumol.kg-1.min-1 was considered insulin resistant, and a value greater than this was considered insulin sensitive. The study population consisted of 21 insulin-resistant and 25 insulin-sensitive black NIDDM patients and 89 normal, nondiabetic black control subjects from an urban hospital. HLA typing was performed with serological methods. RESULTS: The frequency of HLA-DQW7 in the insulin-resistant population (76%) was significantly greater than that in the insulin-sensitive population (32%, corrected P < 0.018) and the normal control population (21%, corrected P < 0.001). The frequency of HLA-DQW6 was increased in the insulin-sensitive population (76%), corrected P < 0.023, as compared with the normal control subjects (33%). The relative risk of HLA-DQW7 in identifying insulin-resistant NIDDM patients compared with control subjects was 7. CONCLUSIONS: At least one component that differentiates insulin-resistant and insulin-sensitive NIDDM in black Americans is under different genetic control. One or more loci responsible for insulin-resistant and insulin-sensitive NIDDM are likely to be in linkage disequilibrium with the DQ locus of the human MHC region of chromosome 6.

Alleles↗
PubMed1992

Oral antidiabetic agents. The emergence of alpha-glucosidase inhibitors.

Hyperglycaemia in patients with non-insulin-dependent diabetes mellitus (NIDDM) results from impaired insulin action and/or deficient insulin secretion. These abnormalities lead to increased hepatic glucose production, the primary cause of fasting hyperglycaemia, and decreased peripheral glucose uptake, the major mechanism responsible for postprandial hyperglycaemia. Hyperglycaemia in patients with NIDDM can be decreased by several different mechanisms: (1) a decrease in nutrient ingestion; (2) an increase in insulin secretion; (3) a decrease in hepatic glucose production; (4) an increase in peripheral glucose uptake. Oral agents used to treat NIDDM operate through 1 or more of the above mechanisms. alpha-Glucosidase inhibitors, a new class of drugs that delay carbohydrate digestion and absorption, reduce postprandial glycaemic rises by about 3 mmol/L. Metformin decreases fasting and postprandial hyperglycaemia through increasing glucose uptake and perhaps decreasing appetite. Sulphonylureas lower hyperglycaemia by increasing insulin secretion and to a lesser degree potentiating insulin action on the liver and peripheral tissues. alpha-Glucosidase inhibitors are particularly useful as primary therapy for patients with mild to moderate hyperglycaemia and in those patients who may be at risk for hypoglycaemia or lactic acidosis. Sulphonylureas are indicated for the more severely hyperglycaemic NIDDM patients who are not yet candidates for insulin therapy. Metformin is useful in obese moderately hyperglycaemic NIDDM patients. These oral agents can be used in combination to give better glycaemic control than is possible with each alone.

Administration, Oral↗
PubMed1992

Insulin action in black Americans with NIDDM.

OBJECTIVE: To assess the influences that obesity and hyperglycemia have on insulin action in black NIDDM patients. RESEARCH DESIGN AND METHODS: Thirty-nine subjects were studied who had normal GHb levels and/or FPG less than 6.4 mM and who had not taken pharmacological agents for 2-91 mo before the study. Insulin action was studied using the euglycemic insulin clamp with a D-[3-3H]glucose infusion. Degree of obesity was assessed with BMI. During carefully monitored follow-up, 9 patients relapsed into a hyperglycemic state, and insulin action was restudied after acute reregulation of their plasma glucose. RESULTS: Insulin action was related to the degree of obesity at the extremes of BMI: 7 of 8 patients (87.5%) with a BMI less than 24.0 kg/m2 were insulin sensitive, and 8 of 9 patients (88.9%) with a BMI greater than 28.5 kg/m2 were insulin resistant. In the midrange BMI (24.0-28.5 kg/m2), patients were equally likely to be insulin resistant or insulin sensitive. A plot of frequency versus glucose disposal in those patients was compatible with a bimodal distribution (P less than 0.025): 12 of 22 patients were normally insulin sensitive (glucose disposal 6.1-9.4 mg.kg-1.min-1), and 10 were insulin resistant (glucose disposal 2.4-4.8 mg.kg-1.min-1). Analysis of this midrange BMI group showed that in the insulin-sensitive group, an inverse relationship existed between BMI and glucose disposal (r = -0.64, P less than 0.05), whereas no such relationship was found in the insulin-resistant group. The clinical characteristics of the midrange BMI group indicated that fasting plasma insulin, total cholesterol, and triglycerides were higher; whereas BMI, age, and FPG were not different in the insulin-resistant compared with the insulin-sensitive group. With the development of hyperglycemia, insulin action in the insulin-sensitive group. With the development of hyperglycemia, insulin action in the insulin-sensitive group was decreased, independent of obesity, whereas it was unchanged in the insulin-resistant group. CONCLUSIONS: Insulin resistance exists in only approximately 50% of black NIDDM patients. The relationship between obesity and insulin resistance is not a simple one. The data can be explained by one of two hypotheses: 1) insulin resistance in black NIDDM patients is an acquired defect related to the development of obesity and is modulated by hyperglycemia, or 2) NIDDM exists as two variants, one with primary insulin resistance and one with normal insulin sensitivity, and that insulin resistance causes central and/or generalized obesity.

Black People↗