Modifications of glucose storage and oxidation in nonobese diabetics, measured by continuous indirect calorimetry.

A new application of continuous indirect calorimetry is described for measuring the disposal of a glucose load. In a group of 10 normal subjects, 3 h after a 100 g oral glucose load, 20 g glucose was oxidized at basal rate, 19 g in response to the load and 63 g stored, while a decrease of 2 g was observed in the glucose space (GS). In a group of four type I, insulin-dependent diabetics, both glucose oxidation (9 g at the basal rate and 4 g in response to the load) and glucose storage (9 g) were markedly decreased, with the remainder either being lost in the urine (36 g) or remaining in the glucose space (42 g). In a group of eight nonobese type II, non-insulin-dependent diabetics, glucose oxidation both in the basal rate and in response to the load was slightly decreased (13 and 14 g, respectively) and glucose storage decreased to 40 g. These results suggest that, in type I diabetics, complete insulin deficiency seriously impairs two major mechanisms regulating glucose homeostasis, i.e., glucose storage and oxidation, while, in type II diabetics, the remaining insulin secretion attentuates these disturbances.

Role of lipid oxidation in pathogenesis of insulin resistance of obesity and type II diabetes.

Increased lipid oxidation is generally observed in subjects with obesity and diabetes and has been suggested to be responsible for the insulin resistance associated with these conditions. We measured, by continuous indirect calorimetry, lipid and glucose oxidation and nonoxidative glucose disposal in 82 obese subjects during a 100-g oral glucose tolerance test (OGTT) and in 26 during a euglycemic insulin (40 mU.min-1.m-2) clamp. The obese subjects were subdivided into those with normal glucose tolerance (group A), those with impaired glucose tolerance (group B), and those with overt diabetes (group C). Forty-five healthy nonobese subjects were subdivided into a young and an older control group, which were age-matched to the nondiabetic obese (groups A and B) and diabetic obese (group C) subjects, respectively. In the postabsorptive state, as well as in response to insulin stimulation (both OGTT and insulin clamp), lipid oxidation was significantly increased in all three obese groups in comparison with either young or older controls. Basal glucose oxidation was significantly decreased in obese nondiabetic and obese glucose--intolerant subjects (groups A and B) compared with age-matched controls. During the OGTT and during the insulin clamp, insulin-stimulated glucose oxidation was decreased in all three obese groups. In contrast, nonoxidative glucose disposal was markedly inhibited in nondiabetic and diabetic obese patients during the euglycemic insulin clamp but not during the OGTT. After glucose ingestion, nonoxidative glucose uptake was normal in nondiabetic obese and glucose-intolerant obese subjects and decreased in diabetic obese subjects. Statistical analysis revealed that lipid and glucose oxidation were strongly and inversely related in the basal state, during euglycemic insulin clamp, and during OGTT. The negative correlation between lipid oxidation and nonoxidative glucose uptake, although significant, was much weaker. Fasting and post-OGTT hyperglycemia were the strongest (negative) correlates of nonoxidative glucose disposal in both single and multiple regression models. We conclude that 1) reduced glucose oxidation and reduced nonoxidative glucose disposal partake of the insulin resistance of nondiabetic obese and diabetic obese individuals; 2) hyperglycemia provides a compensatory mechanism for the defect in nonoxidative glucose disposal in nondiabetic obese subjects; however, this compensation is characteristically lost when overt diabetes ensues; and 3) increased lipid oxidation may contribute, in part, to the defects in glucose oxidation and nonoxidative glucose uptake in obesity.

Evidence for diminished brain 5-hydroxytryptamine biosynthesis in obese diabetic and non-diabetic humans.

Obese persons are often reported to have marked cravings for simple carbohydrate-rich foods. Because of the proposed relationships between protein/carbohydrate selection, plasma tryptophan (TRP) to large neutral amino acids (LNAA) ratios, and brain 5-hydroxytryptamine (5-HT) neurotransmission, we examined the plasma TRP/LNAA ratios in four categories of obese subjects, before and 120 min after oral glucose tolerance test (GTT). Plasma TRP/LNAA ratios were reduced in obese, non-diabetics by 18%, the same extent as for older (approximately 52 yr old) nonobese subjects. In more advanced obesity, ie obesity associated either with glucose intolerance, hyperinsulinemia or hypoinsulinemia, plasma TRP/LNAA ratios were reduced by 25%. One hundred twenty minutes after a 100 g glucose load plasma TRP/LNAA had not been normalized. Based on animal data, these results suggest there may be diminished 5-HT neurotransmission in obese diabetics. The implications of these findings for the cravings of obese for carbohydrate-rich foods is discussed.

Study on lipid metabolism in obesity diabetes.

Knowing the relationship between obesity and diabetes, the purpose of our work was to study the alterations in lipid metabolism as measured by continuous indirect calorimetry in the course of a 100-g oral glucose-tolerance test in groups of obese patients without and with diabetes, respectively. Seventy-nine obese patients participated in the study. They were divided into four groups according to the degree of carbohydrate intolerance: group A, normal glucose tolerance; group B, impaired glucose tolerance; group C, diabetes with hyperinsulinemic response to the load; group D, diabetes with impaired insulin response. All four groups of patients presented an increase in lipid oxidation, both in the fasting state and during the three-hour glucose tolerance test, when compared to the control group. The lipid oxidation rate was roughly parallel to plasma free fatty acid (FFA) levels. The contribution of lipids to energy expenditure was higher in obese as compared to control subjects. These observations suggest that the larger part taken by lipids in the energy metabolism of both nondiabetic and diabetic obese humans is a consequence of their increased fat stores and that the resulting decrease in carbohydrate metabolism may lead, as a late consequence, to alterations in glucose tolerance. The latter may result in delayed glucose storage and oxidation in the obese patient.

Comparison of glucose, fructose, sorbitol, and xylitol utilization in humans during insulin suppression.

During fructose, sorbitol, and xylitol perfusions, carbohydrate utilization was studied by continuous indirect calorimetry and compared with glucose utilization during pharmacologic inhibition of endogenous insulin secretion. The experiment was performed in 28 normal volunteers divided into 5 groups (glucose, fructose, sorbitol, xylitol, and saline), each subject being its own control. Insulin suppression was obtained by means of a constant infusion of epinephrine (6 microgram/min) and propranolol (0.08 mg/min). After 90 min, during plasma insulin steady state, each sugar or polyol was infused at a rate of 6 mg/kg/min for 120 min. In contrast with a rise in plasma glucose from 161 +/- 6 mg/dl) to 291 +/- 14 mg/dl during glucose infusion, glucose levels remained unchanged during infusion of the glucose substitutes. Carbohydrate oxidation showed a rise of 24, 65, 76, and 44 mg/min during infusions of glucose, fructose, sorbitol, and xylitol, respectively. Lipid oxidation rates decreased by 7, 20, 33, and 23 mg/min during the same infusions. These results indicate that fructose, sorbitol, and xylitol are oxidized at a higher rate than glucose during suppression of endogenous insulin secretion, without any significant rise in glycemia.

Obesity: a maternal high-risk factor.

In reviewing maternal mortality in Minnesota over the last 10-year period, obesity proved to be a major high-risk factor to the parturient. In the following report 12 per cent of the study group weighed over 200 lb in the nonpregnant state. Pulmonary embolism was the leading cause of death in obese group. Obstetricians are encourged to recognize the possible complications that obesity poses in the pregnancy period.

The comparative oxidation of glucose, fructose, sorbitol and xylitol in normal man.

The aim of the study was to compare the effects of fructose, sorbitol and xylitol with those of glucose on blood glucose and insulin levels and carbohydrate utilization in man. The experiment was performed by means of continuous indirect calorimetry in five groups of five to six normal volunteers during infusion of either glucose, fructose, sorbitol, xylitol or a mixture of fructose, glucose and xylitol in the proportion of 2:1:1. Glucose and insulin did not present any important variations during the fructose, sorbitol and xylitol infusiosns. However, carbohydrate oxidation rose significantly during administration of these substrates. Carbohydrate oxidation rose 80 mg/min for fructose, 27 mg/min for sorbitol, 39 mg/min for xylitol and 75 mg/min for the carbohydrate mixture, in comparison to 101 mg/min for glucose. It is concluded that fructose, sorbitol and xylitol provoke an increase in carbohydrate utilization without a corresponding rise in glycemia and insulinemia.

A controlled study of the exocrine pancreatic function in Sjögren's syndrome and rheumatoid arthritis.

The exocrine pancreatic function has been estimated using the N-benzoyl-L-Tyrosyl para-amino-benzoic acid test (NBT PABA test) and by measuring the trypsinemia by radio-immunoassay (RIA trypsinemia) in nonselected cases of Sjögren's syndrome (SS) and seropositive rheumatoid arthritis (RA) in comparison with normal controls. The NBT PABA test was pathological in 37,5% of SS and 35% of RA patients but in none of the controls. The RIA trypsinemia was found to be high in 6,2% of SS and 45% of RA patients. These findings suggest that exocrine pancreatic function is impaired in some SS and RA cases. However, this exocrine pancreatic defect was clinically silent in all patients.

A comparative multicentre trial of halometasone/triclosan cream and diflucortolone valerate/chlorquinaldol cream in the treatment of acute dermatomycoses.

In this multicentre, between-patient trial the efficacy and tolerability of a cream, containing 0.05% halometasone and 1% triclosan, was compared with those of Nerisona C cream, containing 0.1% diflucortolone valerate and 1% chlorquinaldol, in 183 patients with acute dermatomycoses. Halometasone/triclosan cream and the comparative cream showed closely similar results with respect to good to very good therapeutic effects (60% versus 57%). However, halometasone/triclosan cream proved superior to the comparative preparation with regard to very good (cured) results (53% versus 46%), an early cure in less than 30 days (41% versus 34%) and onset of action within 3 days of starting the treatment (32% versus 18%). Mycological findings were positive on direct microscopy in 36% and 43% and in culture in 19% and 17% of the patients following treatment with halometasone/triclosan cream and the comparative cream preparation, respectively. Adverse effects were reported in seven out of 108 patients treated with halometasone/triclosan cream and in five out of 107 patients treated with the comparative preparation.

Diabetes in pregnancy. No longer a barrier to successful outcome.

There are three key goals in current management of the diabetic pregnancy. Normal diabetes control before conception and during the first trimester in an attempt to reduce the incidence of congenital abnormalities. This implies that all diabetic women of childbearing age should have counseling before pregnancy. Routine use of new techniques such as home blood glucose monitoring, intensified conventional insulin regimens, or an insulin infusion pump for maintenance of tight metabolic control both before and during pregnancy. Delay in delivery of the baby until the due date, assuming good diabetes control and normal antepartum monitoring of the fetus, to reduce the incidence of macrosomatia, decrease the rate of cesarean section, and decrease neonatal mortality. The current outlook for the pregnant woman with diabetes is an optimistic one. Until recently, most women with diabetes were told that they should avoid pregnancy. Sterilization was often suggested as a means of contraception. Unfortunately, some women are still getting that message from their physician. This is unacceptable, as it is obvious that diabetes is no longer a barrier to pregnancy. Most women with diabetes can now consider the possibility of pregnancy and know that they have a reasonable chance of having a healthy child. Furthermore, new developments in diabetes care continue and should lead to an even brighter future for this group of patients. New advances in treatment, such as implantable insulin pumps, glucose sensors, and islet cell transplants, are just over the horizon. With these developments, a woman with diabetes will be freed from the intensive regimen she must now practice to achieve a successful pregnancy.