Bernardo Léo Wajchenberg

Metabolic Effects of Dietary Sucrose and Fructose in Type II Diabetic Subjects

OBJECTIVE To investigate the metabolic effects of dietary fructose and sucrose in type II diabetic patients. RESEARCH DESIGN AND METHODS Sixteen well-controlled type II diabetic subjects were fed three isocaloric diets for 28 days each. The three diets provided 50–55, 15, and 30–35% of total energy from carbohydrate, protein, and fat, respectively. In one diet, 20% of total calories were derived from fructose; in another, 19% of total calories were derived from sucrose; and in the control diet, only 5% of daily calories were derived from sugars, all other carbohydrates being supplied as polysaccharides. RESULTS No significant differences were observed between either the fructose or the sucrose diet and the control polysaccharide diet in any of the measures of glycemic control, serum lipid levels, or insulin and C-peptide secretion. CONCLUSIONS Our data suggest that in the short and middle terms, high fructose and sucrose diets do not adversely affect glycemia, lipemia, or insulin and C-peptide secretion in well-controlled type II diabetic subjects.

A study of patients with Nelson's syndrome

The prevalence of Nelsons syndrome has varied greatly, at least in part because of the variability of the diagnostic criteria employed by different authors. We define Nelsons syndrome as the presence of an enlarging pituitary tumour associated with elevated fasting plasma ACTH levels and hyperpigmentation in patients with Cushings disease after bilateral adrenalectomy. We have compared patients with Cushings disease who developed Nelsons syndrome after bilateral adrenalectomy with those who did not. Our objective was to find differences between the two groups which might predict the development of Nelsons syndrome.

Salivary cortisol for the evaluation of Cushing's syndrome

Cortisol concentrations were measured in matched plasma and salivary samples from 8 healthy controls, 8 patients with Cushings syndrome and 4 patients suspected of having spontaneous hypercortisolism. In healthy subjects, the circadian rhythm in salivary cortisol paralleled that in plasma. Absence of the diurnal rhythm in Cushings syndrome was seen in saliva as well as in plasma. After ACTH stimulation, mean peak cortisol in saliva showed a 3-fold increase while in plasma there was a 2.5-fold increment above baseline. Cushings syndrome, due to pituitary or adrenal adenoma was diagnosed equally well by measuring the cortisol response to cosyntropin in either plasma or saliva. Finally, the low- and high-dose dexamethasone suppression test was reflected equally well in both plasma and saliva. In patients suspected of having Cushings syndrome dynamic tests can be performed in both plasma and saliva. However, in some samples, the salivary cortisol measurement appears advantageous over plasma cortisol determination.

Effect of a sulfonylurea (gliclazide) treatment on insulin sensitivity and glucose-mediated glucose disposal in patients with non-insulin-dependent diabetes mellitus (NIDDM)

Five male non-obese newly diagnosed NIDDM and 5 age-, sex- and body mass index (BMI) matched healthy controls without a family history of diabetes were submitted to a frequently sampled intravenous (i.v.) glucose tolerance test modified by exogenous insulin administration for estimation of insulin sensitivity (SI) and glucose-mediated glucose disposal (SG) with Bergmans minimal model computer analysis of glucose kinetics. The tests were repeated after 3 months treatment with a second generation sulfonylurea, gliclazide, in the diabetics subjects. SI and SG were markedly reduced before gliclazide therapy in the diabetics in comparison to the paired controls. After gliclazide, despite significantly lower (almost normal) plasma glucose, normalization of glycosylated hemoglobin and increased fasting insulin levels, there was a slight but significant increase in SI while SG showed a further reduction, the improvement in glucose control being also associated to the significant increased first and 2nd phase insulin release for the first 20 min after glucose infusion.

ACANTHOSIS NIGRICANS, HIRSUTISM, INSULIN RESISTANCE AND INSULIN RECEPTOR DEFECT

A 24‐year‐old negress with the triad of acanthosis nigricans, hirsutism associated with polycystic ovaries and insulin resistance is reported. Metabolic studies were done 3 years after a bilateral ovarian wedge resection. Partial remission of the hirsutism and return of menstrual cycles occurred after surgery. Extreme resistance to endogenous and exogenous insulin was observed. Three studies of insulin receptors on circulating red blood cells (RBC) showed abnormal inhibition‐competition curves, characterized by increased percentage insulin binding at higher unlabelled insulin levels. Scatchard plots suggested an apparent increase in the number of low affinity receptors. Despite the changes in receptor‐insulin interaction, the defect does not seem to explain the insulin resistance since binding of insulin to a target tissue (RBC) appeared to be quantitatively normal at physiological insulin levels, suggesting a simultaneous post receptor defect.

Effects of adrenergic stimulating and blocking agents on glucose-induced insulin responses in human thyrotoxicosis.

Abstract The effects of thyroid hormone excess on insulin responses to a constant glucose infusion ( 300 mg min/60 min ) were studied in five adult thyrotoxic patients with Graves disease before and after they had attained euthyroidism. The tests were also performed during administration of isoproterenol (0.05 μg/kg body weight/min), propranolol (0.08 mg/min) and phentolamine (0.5 mg/min). In the control experiments, to similar plasma glucose, thyroid hormone excess was accompanied by higher fasting plasma insulin, suggesting an insulin resistant state. During glucose infusion, to similar glucose increments, insulin concentration increased in both hyper and euthyroid states, differences in concentration observed in the fasting state disappearing during the infusion, suggesting either reversal of the insulin resistant state and/or decreased insulin responses in the hyperthyroid state. During isoproterenol administration, thyroid hormone excess induced disproportionally higher insulin responses to glucose, suggesting that β-stimulation and thyroid hormone exerted agonistic actions. During propranolol administration, thyroid hormone excess counteracted the β-adrenergic blockade effect in decreasing insulin secretion, suggesting that thyroid hormone and β-adrenergic blockade presented antagonistic effects. During phentolamine administration, apart from its effect by itself, no apparent action of thyroid hormone excess on insulin responses to glucose could be demonstrated. The results suggest that thyroid hormone influences on glucose-induced insulin responses are apparently agonistically interrelated to the β-adrenergic tonus of the patients.

Tecido adiposo como glândula endócrina

The author has studied the hormonal secretion by the adipose tissue, related to fat metabolism, blood coagulation, steroids and energetic balance, such as leptin and adiponectin, and autocrine-paracrine relationships.

Glycemia and cardiovascular disease in type 1 diabetes mellitus.

OBJECTIVE To evaluate the role of glycemic control in the development of cardiovascular disease (CVD) in type 1 diabetes mellitus (DM). METHODS We review the literature regarding coronary atherosclerosis, coronary artery calcification, and the epidemiologic studies related to the role of glycemia and the classic risk factors for coronary artery disease (CAD) in type 1 DM. RESULTS Four prospective studies (Wisconsin Epidemiologic Study of Diabetic Retinopathy, EURODIAB, Steno Diabetes Center Study of Adults With Type 1 DM, and Pittsburgh Epidemiology of Diabetes Complications study) do not show that glycemic control predicts CAD occurrence. Findings from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study show that compared with conventional insulin therapy, intensive insulin therapy reduces CVD among patients with type 1 DM and is associated with lower prevalence of coronary artery calcification. The discrepancies between the findings from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study and the Pittsburgh Epidemiology of Diabetes Complication study are likely due to differences between the study populations and the lower prevalence of renal disease in the former study. Besides duration of DM and albuminuria/overt nephropathy, insulin resistance is a major determinant of CAD associated with type 1 DM. CONCLUSIONS Discrepant study results regarding the relationship between glycemia and CAD/coronary artery calcification may be related to the prevalence of renal disease and the presence of the metabolic syndrome. Published data suggest that addressing traditional risk factors including albuminuria, the metabolic syndrome, and inflammatory markers is better for preventing and treating CAD than focusing exclusively on glycemic control, which is still necessary for preventing microvascular complications. Furthermore, there is a synergistic effect of glycemic control and albuminuria on the development of CVD.

Treatment of Adrenocortical Cancer with O,P′-DDD

Excerpt The initial observations of Nelson and Woodward (1, 2) that the feeding of the insecticide, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethane (DDD) to dogs results in necrosis and atrophy of the...

The natural history of diabetic nephropathy in type I diabetes and the role of metabolic control in its prevention, reversibility and clinical course

SummaryThe authors present a contemporary picture of the pathogenesis and clinical course of diabetic nephropathy in type I diabetics describing the stages of the disease and the possible evidence for reversibility of the kidney damage with tight metabolic control. During the socalledlatency period, which is clinically non-detectable, the predominant functional abnormalities (increase in GFR with sub-clinical glomerular proteinuria) can be corrected by strict control although there is no evidence for the regression of the associated anatomical changes such as the enlarged filtration area. As for the described increase in thickness of the glomerular basement membrane, from experimental data and pancreatic transplants in man, delay in its development and to some extent regression of the glomerular lesions can be expected. The problem of how the renal lesions in experimental diabetes mirror the changes in the human kidney is discussed. During thesymptomatic period, with intermittent and subsequently constant proteinuria and progressive decline in renal function, which are observed in only about 30% of type I diabetics, the role of arterial hypertension and its effective control is emphasized. Finally, therenal failure period is indicative of irreversible damage to the kidneys. The progression from its early to its late stages is variable between different patients but each individual patient shows a constant rate of deterioration. The evidence for the efficacy of medical treatment in slowing down its progression is very limited at present but much can be done to improve the quality of life by dietary measures, treatment of fluid overload and hypertension. When the end-stage diabetic kidney disease is reached, with serum creatinine above 8 mg/dl, renal transplantation from a living donor offers a good chance for a relatively acceptable quality of life for years. In conclusion, it is stressed that the morbidity of diabetic nephropathy could eventually be reduced through effective control of the metabolic abnormalities of diabetes with the methods presently available.