Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians.

Previous studies have shown that Asian Indians (AIs) are insulin resistant and at high risk for developing diabetes and coronary heart disease, compared with Caucasians. To examine whether differences in body fat distribution contribute to this risk, 12 healthy AIs and 12 Caucasians matched for age and body mass index (BMI) underwent a 75-g oral glucose tolerance test, 2-h euglycemic hyperinsulinemic clamp, abdominal (L2-3) computed tomography scan, and fasting lipid and plasminogen activator inhibitor-1 (PAI-1) levels. Despite similar fasting plasma glucose levels, AIs exhibited fasting hyperinsulinemia (P = 0.001), higher glucose (P = 0.03) and insulin (P = 0.004) levels during the oral glucose tolerance test, and reduced glucose disposal rate (R(d)) (4.7 +/- 0.4 vs. 7.5 +/- 0.3 mg/kg per min, P < 0.0001) during the clamp. AIs had significantly lower high-density lipoprotein, higher low-density lipoprotein, and significantly higher PAI-1 levels (P = 0.01). Despite similar BMI, AIs had significantly greater total abdominal fat (P = 0.04) and visceral fat (P = 0.04). In all subjects, measures of fat mass were inversely correlated with R(d) during the clamp (r = -0.47 to -0.61, P < 0.01-0.001). Visceral fat mass was correlated with triglycerides, low-density lipoprotein, and high-density lipoprotein (P < 0.002-0.0001). PAI-1 was inversely correlated with R(d) in AIs (r = -0.70, P < 0.01) and not in Caucasians (r = -0.24, P = 0.44). For comparable BMI and age, healthy AIs have physiologic markers for insulin resistance, dyslipidemia, and increased cardiovascular risk, compared with Caucasians. Alterations in body fat distribution--particularly increased visceral fat--may contribute to these abnormalities.

A new educational approach for supporting the professional development of third-year medical students.

This paper describes a new course designed to support the professional development of third-year medical students. The course runs through the clinical clerkships, and has several additional features: it includes a multidisciplinary faculty; it is centrally based in the medical school; it addresses students' values and attitudes in addition to their knowledge and skills; and it makes use of small-group learning methods, and faculty, student, and group continuity during the year. The curriculum, which addresses ethical, social, and communicative issues in medicine, plus the evaluation of students and of the course, are described.

A prospective study of postmenopausal estrogen therapy and subsequent incidence of non-insulin-dependent diabetes mellitus.

The potential influence of postmenopausal estrogen therapy on the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM) is relatively unexplored, despite postulated effects of these hormones on glucose tolerance. We examined the association between postmenopausal hormone use and the subsequent incidence of NIDDM in a prospective cohort of 21,028 postmenopausal US women aged 30 to 55 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1976. During 12 years of follow-up (422,991 person-years), we confirmed 1249 cases of NIDDM. Current users of postmenopausal hormones had a relative risk of NIDDM of 0.80 (95% confidence interval, 0.67 to 0.96) as compared with never users, after adjustment for age and body mass index (BMI). Past users of these hormones had an age- and BMI-adjusted relative risk of 1.07 (0.93 to 1.23). These results were not materially altered by multivariate adjustment for age, BMI, family history of diabetes, and coronary risk factors. Comparable results were obtained when the analysis was restricted to symptomatic NIDDM as the outcome. We observed no appreciable modification of these associations by family history of diabetes or category of BMI. Duration of current or past use of postmenopausal hormones and dose of conjugated estrogen were not significantly related to incidence of NIDDM. Type of hormone (estrogen alone, progesterone alone, or combination) also did not appear to influence NIDDM risk. These prospective data indicate that postmenopausal hormone therapy is unlikely to be associated with a material increase in the incidence of NIDDM among women.

Parity and incidence of non-insulin-dependent diabetes mellitus.

PURPOSE: To examine prospectively the association between parity and subsequent incidence of non-insulin-dependent diabetes mellitus (NIDDM). Most previous studies have not controlled for potential confounding by age and obesity. PATIENTS AND METHODS: In a prospective cohort study, 113,606 United States registered nurses aged 30 to 55 years and free of diagnosed diabetes, coronary heart disease, stroke, and cancer at baseline were followed for 12 years. Endpoint was incidence of confirmed NIDDM. RESULTS: During 1,278,188 person-years of follow-up, we confirmed 2,310 incident cases of NIDDM. An apparent association between parity and diabetes was observed in unadjusted analyses (relative risk = 1.56 [95% confidence interval (CI), 1.27 to 1.91] among women with six or more births compared with that in nulliparous women) (p, trend less than 0.00001). This association was attenuated after adjustment for age (relative risk = 1.19 [CI 0.97 to 1.48], p, trend = 0.06) and was completely abolished after adjustment for both age and body mass index (relative risk = 0.95 [CI 0.75 to 1.19], p, trend = 0.19). Multivariate adjustment for family history of diabetes, age at first birth, hormone use, and other variables did not materially alter these findings. There was no important modifying effect of family history of diabetes on these associations. CONCLUSIONS: Despite a temporary diabetogenic effect of pregnancy, parity is not associated with an increased risk of subsequent clinical NIDDM. These data underscore the importance of control for confounding by age and obesity in evaluating these associations.

A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women.

We examined the relationship of maturity-onset clinical diabetes mellitus with the subsequent incidence of coronary heart disease, stroke, total cardiovascular mortality, and all-cause mortality in a cohort of 116,177 US women who were 30 to 55 years of age and free of known coronary heart disease, stroke, and cancer in 1976. During 8 years of follow-up (889 255 person-years), we identified 338 nonfatal myocardial infarctions, 111 coronary deaths, 259 strokes, 238 cardiovascular deaths, and 1349 deaths from all causes. Diabetes was associated with a markedly increased risk of nonfatal myocardial infarction and fatal coronary heart disease (age-adjusted relative risk [RR] = 6.7; 95% confidence interval [CI], 5.3 to 8.4), ischemic stroke (RR = 5.4; 95% CI, 3.3 to 9.0), total cardiovascular mortality (RR = 6.3; 95% CI, 4.6 to 8.6), and all-cause mortality (RR = 3.0; 95% CI, 2.5 to 3.7). A major independent effect of diabetes persisted in multivariate analyses after simultaneous control for other known coronary risk factors (for these end points, RR [95% CI] = 3.1 [2.3 to 4.2], 3.0 [1.6 to 5.7], 3.0 [1.9 to 4.8], and 1.9 [1.4 to 2.4], respectively). The absolute excess coronary risk due to diabetes was greater in the presence of other risk factors, including cigarette smoking, hypertension, and obesity. These prospective data indicate that maturity-onset clinical diabetes is a strong determinant of coronary heart disease, ischemic stroke, and cardiovascular mortality among middle-aged women. The adverse effect of diabetes is amplified in the presence of other cardiovascular risk factors, many of which are modifiable.

Teaching medicine as a human experience: a patient-doctor relationship course for faculty and first-year medical students.

We developed a required, longitudinal course for first-year medical students that addressed the patient-doctor relationship. Our course linked understanding patients' experiences and perspectives on illness with listening to, talking with, and establishing a rapport with patients while obtaining their medical histories. Learning was enhanced by use of an interdisciplinary faculty and by small-group continuity and faculty mentoring. Our curriculum adapted problem-based, self-directed educational methods to convey medical humanism. We focused on bedside interviewing as the means for exploring patients' social, emotional, and ethical concerns.

Weight as a risk factor for clinical diabetes in women.

To determine the relation of body mass index (weight/height2) with the risk of clinical non-insulin-dependent diabetes, the authors analyzed data from a cohort of 113,861 US women aged 30-55 years in 1976. During 8 years of follow-up (826,010 person-years), 873 definite cases were identified among women initially free from diagnosed diabetes. Among women of average body mass index, 23-23.9 kg/m2, the relative risk was 3.6 times that of women having a body mass index less than 22 kg/m2. The risk continued to increase above this level of body mass index. The authors observed a much weaker positive association with weight at age 18, and this association was eliminated after adjustment for current body mass index. Thus, weight gain after age 18 was a major determinant of risk. For an increase of 20-35 kg, the relative risk was 11.3, and for an increase of more than 35 kg, the relative risk was 17.3. Adjusting for family history did not appreciably alter the strong relation observed among women at average levels of body mass index. These data indicate that, at even average weight, women are at increased risk of clinical non-insulin-dependent diabetes and that the relation between body mass index and risk of diabetes is continuous.

Hypoglycemia associated with liver disease and ethanol.

The liver is key to glucose homeostasis. Any disruption of its metabolism, structural integrity, or intracellular dynamics may alter the liver's ability to maintain normal glucose homeostasis. When such disruption affects hepatic glucose output, hypoglycemia may eventuate. Multiple drugs including alcohol may alter the intrahepatic pathways that are vital for normal glucose production by the liver. Spontaneous hypoglycemia always warrants an evaluation of hepatic function and a careful scrutiny of medications that affect hepatic structural or biochemical integrity.

A prospective study of moderate alcohol drinking and risk of diabetes in women.

Several investigators have observed an association between alcohol consumption and elevated glucose levels, raising the possibility that alcohol may increase the risk of diabetes. This hypothesis was evaluated prospectively among 85,051 women participating in the Nurses' Health Study who were 34 to 59 years of age in 1980 and had no history of cancer, coronary heart disease, or diabetes. At baseline, participants completed an independently validated dietary questionnaire which included information on the consumption of beer, wine, and liquor. Incident cases of non-insulin-dependent diabetes were reported on follow-up questionnaires sent in 1982 and 1984 (98% response to at least one follow-up); 526 cases were confirmed by a supplementary questionnaire regarding symptoms, laboratory values, and treatment. The risk of diabetes decreased monotonically with increasing alcohol consumption (chi trend = -9.4, p less than 0.0001). Compared with nondrinkers, women consuming 5-14.9 g of alcohol per day (about 4-10 drinks per week) had an age-adjusted relative risk of diabetes of 0.4 (95% confidence interval (CI) 0.3-0.6); for 15 g or more per day, the relative risk was 0.3 (95% CI 0.2-0.4). However, a strong inverse association between alcohol drinking and body weight explained much of the apparent protective effect of alcohol. After simultaneous adjustment for Quetelet index (weight (kg)/height (m)2), family history of diabetes, total caloric intake, and age, the relative risk of diabetes for consumers of 5-14.9 g per day was 0.8 (95% CI 0.6-1.2), and for women who drank 15+ g per day, the relative risk was 0.6 (95% CI 0.3-0.9). These data provide no support for the hypothesis that moderate alcohol intake increases the risk of non-insulin-dependent diabetes.

Nutrition therapy for the child and adolescent with Type I diabetes mellitus.

The author enumerates the objectives of nutritional instruction and therapy for the child with diabetes mellitus and examines some of the principles upon which this therapy is based. Also discussed are the methods used to formulate meal plans, stressing the fact that instruction and counseling in nutritional principles is a continuous process that must be enthusiastically supported by the pediatrician and the physician who follows the diabetic patient during adult life.

Current principles of dietary therapy of diabetes mellitus.

"Diet therapy" is a term with multiple implications. Current concepts, and the principles upon which they are based, are examined, and an attempt is made to elaborate diet therapy in the context of the pathogenesis of diabetes.

Diet and diabetes mellitus: concepts and objectives.

Diabetes mellitus is a complex disease with two dominant pathogenic lesions, one resulting from a failure of the beta cells of the islets of Langerhans and the other from resistance to the actions of insulin in peripheral tissue. Patients may demonstrate varying degrees of either or both lesions. Diet has an important place in the treatment of all diabetics. The most important objective is control of total caloric intake to attain and maintain ideal body weight. Obesity is diabetogenic. The diet of children with diabetes should allow them to grow and develop normally. Insulin-dependent diabetics must eat meals on a regular schedule. Carbohydrate intake should not be disproportionately restricted. Fat intake in diabetics and in nondiabetics should comprise only about 30% of total calories. Dietary instruction should not be a one-time affair. Physicians should seek the assistance of diet counselors when they are available. Many basic questions about diet and diabetes remain unanswered.

Effect of starvation on the production and metabolism of thyroxine and triiodothyronine in euthyroid obese patients.

The metabolic clearance and production rates of thyroxine (T4) and triiodothyronine (T3) were measured in 9 obese euthyroid patients prior to and during prolonged starvation. The metabolic clearance rates (MCR) and serum concentrations of T4, and, therefore, the metabolic degradation or production rates of T4 were unchanged during starvation. Serum T3 concentrations decreased strikingly during starvation, from 145 +/- 7 ng/dl (mean +/- SE) to 66 +/- 9 ng/dl (P < 0.001), while the mean MCR of T3 was unchanged, with the result that T3 degradation or production rates were markedly decreased (36.4 +/- 4.5 µg/d vs. 11.2 +/- 0.7 µg/d; P < 0.001). These findings suggest that the decrease in serum T3 concentration observed during starvation results from a decrease in the peripheral conversion of T4 to T3.

Effects of aspartame in young persons during weight reduction.

Given the potential use of a low-calorie sweetener during weight reduction, a toxicity study of chronic aspartame ingestion was conducted. Particular attention was given to possible long-term effects of aspartame on the fuel hormonal alterations characteristically caused by weight reduction. As a group mean age was 19.3 yr, body weight was 164.6 lb, and mean height was 65.4 in. Subjects were an average of 33% in excess of ideal body weight. The aspartame dose was 2.7 g/day and was compared on a double-blind randomized basis with a lactose placebo. Both materials were given in gelatin capsules. An average of 6.9 +/- 1.5 lb was lost by the aspartame group during the 13-wk study on a calculated 1,000-calorie diet. The placebo group lost 4.5 +/- 1.2 lb (no significant difference between the two groups). After an overnight fast, reductions in glucose and immunoreactive insulin were seen in both groups, while rising trends in immunoreactive glucagon were observed. These changes are all characteristic of calorie restriction. In no instance was there a detectable effect of the ingested aspartame. No meaningful effect of weight reduction or aspartame was seen on plasma triglyceride and cholesterol, nor on any other parameter of hematologic, hepatic, or renal function that was measured. Similarly, side effects were equally distributed between asparatame and placebo.

Extreme hypermagnesemia as a cause of refractory hypotension.

A 62-year-old woman with adequate renal function who consumed large quantities of magnesium citrate presented with lethargy and hypotension. The hypotension was refractory to all conventional therapy. Her serum magnesium was 12.5 meq/litre (normal, 1.5 to 2.5). She was found to have a perforated duodenal ulcer; peritoneal aspirate magnesium concentration was 12.2 meq/litre. Hypotension improved with intravenous calcium and peritoneal dialysis. This case shows that hypermagnesemia may be accompanied by severe refractory hypotension, and that intestinal disease may predispose to hypermagnesemia in patients ingesting large quantities of magnesium despite normal renal function. Dialysis removes excess magnesium and reverses its toxic effects.

Lipid metabolism in pregnancy. II. Altered lipid composition in intermediage, very low, low and high-density lipoprotein fractions.

The hyperlipidemia of pregnancy consists primarily of an increase in triglyceride with lesser rises in cholesterol and phospholipid. As a further characterization, we have analyzed all lipids in the major lipoprotein subfractions in fasting pregnant and non-pregnant women. An elevated triglyceride in the major lipoprotein fractions in pregnancy is confirmed. The triglyceride rises in VLDL and IDL (density 1.006-1.019 lipoprotein) are associated with proportional rises in cholesterol and phospholipid. The result is a 3-4-fold increase of compositionally unchanged lipoprotein lipid. Contrasting changes are seen in LDL, density 1.019-1.063 lipoprotein, and HDL. In these fractions, triglyceride rises more than cholesterol and phospholipid. As a result, an increase in triglyceride on a percentage basis tends to reduce the contribution of the other two lipids. Nonetheless, on an absolute basis HDL cholesterol is not significantly reduced. The proportional increases in all lipids of VLDL and IDL fractions are consistent with increased VLDL production in pregnancy as suggested by data from animal systems. However, alterations in removal are not rules out. Maintenance of the HDL cholesterol level distinguishes pregnancy from other endogenous hypertriglyceridemias where HDL cholesterol is reduced. One may speculate that these physiological adaptations in material lipid transport can serve the increased energy needs of the mother, supply steroid hormone precursors for the placenta, and provide cholesterol and essential fatty acids for the fetus.