Charles R. Shuman

External Pancreatic Secretion in Diabetes Mellitus

Excerpt Whether changes in external pancreatic secretion can occur in diabetes mellitus has long been debated. Early investigators, using a single lumen (1) or a double lumen tube (2-4) for the col...

Reduced epinephrine secretion and hypoglycemia unawareness in diabetic autonomic neuropathy.

The cause of susceptibbility of certain diabetic patients to severe hypoglycemia is not known. Because the awareness of hypoglycemia is heightened by catecholamine-mediated physiologic responses, deficient catecholamine secretion may cause frequent and severe hypoglycemia. Plasma epinephrine and norepinephrine were measured after insulin-induced hypoglycemia in 18 diabetic patients, nine with autonomic neuropathy, and in nine normal volunteers. Our results show that two thirds of patients with diabetic autonomic neuropathy have moderate to severe deficits in epinephrine secretion and that these patients have diminished or delayed subjective responses to low blood sugar and are at risk for developing severe hypoglycemia and its neurologic consequences.

Comparative measurements of glucose, beta-hydroxybutyrate, acetoacetate, and insulin in blood and cerebrospinal fluid during starvation.

Abstract The possibility that altered central nervous system (CNS) metabolism is reflected by changes in the constituents of the cerebrospinal fluid (CSF) was investigated. From eight obese subjects undergoing total starvation for weight reduction, overnight and 21-day fasting specimens of venous blood and lumbar CSF were obtained nearly simultaneously to determine the concentrations of glucose, beta-hydroxybutyrate (β-OHB), acetoacetate (AcAc), and immunoreactive insulin (IRI). After 21 days of starvation, the glucose concentration fell in both blood and CSF. The decrease in blood glucose was greater than the decline in CSF glucose, resulting in a diminished blood-CSF difference. Concentrations of β-OHB and AcAc in blood and CSF were elevated after prolonged fasting, but blood levels exceeded those in CSF, producing an increased blood-CSF ketone body difference. After an overnight and 21-day fast, the IRI levels in CSF were about one-half of the serum levels. These data suggest that metabolic alterations in CNS metabolism during prolonged starvation are reflected in substrate concentrations observed in CSF, and demonstrate that insulin is presented in the CSF of man.

Monitoring Metabolic Control in Diabetic Outpatients with Glycosylated Hemoglobin

The usefulness of HbA, as a monitor of metabolic control was studied in 15 diabetic outpatients during periods of stable, deteriorating, and improving control. Mean fasting concentrations of HbA, and plasma glucose during a 3-month period of stable control were 12.6% +/- 0.8% and 120 +/- 8 mg/dL, respectively. One week after discontinuation of oral hypoglycemic therapy, blood glucose had risen to 172 +/- 23 mg/dL and HbA, to 14.1% +/- 0.7% (P less than 0.025). Reinstitution of therapy resulted in a significant fall of blood glucose within 2 weeks. A significant decline in HbA1 (from 15.3% +/- 0.8% to 14.1% +/- 0.9%, P less than 0.025) occurred 2 weeks later. The data show that the rate of formation of HbA1 is considerably faster than its rate of disappearance. Thus, HbA1 is likely to reflect disproportionally recent episodes of poor control. We conclude that HbA1 is useful to monitor diabetic outpatients during periods of stable and rapidly deteriorating control but is not suited to detect rapid metabolic improvements.

Rapid Intravenous Sodium Acetoacetate Infusion in Man METABOLIC AND KINETIC RESPONSES

The metabolic and kinetic responses to rapidly intravenously administered sodium acetoacetate (1.0 mmol/kg body wt) was studied after an overnight fast in 12 male and female adults weighing between 88 and 215% of average body weight. Blood was obtained before, during, and after the infusion for determination of circulating concentrations of immunoreactive insulin, glucose, acetoacetate, beta-hydroxybutyrate and free fatty acids. In three obese subjects the studies were repeated after 3 and 24 days of total starvation. After the overnight fast acetoacetate rose rapidly reaching a peak concentration at the end of the infusion; beta-hydroxybutyrate concentrations also increased rapidly and exceeded those of acetoacetate 10 min postinfusion. Total ketone body concentration at the end of the infusion period was comparable to that found after prolonged starvation. After the initial mixing period, acetoacetate, beta-hydroxybutyrate and total ketone bodies rapidly declined in a parallel manner. There were no obvious differences between the subjects with regard to their blood concentrations of ketone bodies. The mean plasma free fatty acid concentration decreased significantly during the 20th to 90th min postinfusion period; for example the control concentration of 0.61 mmol/liter fell to 0.43 mmol/liter at 60 min. In the three obese subjects studied repeatedly, fasting plasma free fatty acids decreased with acetoacetate infusion from 0.92 to 0.46 mmol/liter after the 3 day fast and from 1.49 to 0.71 mmol/liter after the 24 day fast. Acetoacetate infusion caused no changes in blood glucose concentration after an overnight fast. However, in the three obese subjects restudied after 3- and 24-day fasts blood glucose decreased, respectively, from 3.49 to 3.22 mmol/liter and from 4.07 to 3.49 mmol/liter. The mean serum insulin concentration in all subjects significantly increased from 21 to 46 muU/ml at the completion of the infusion and rapidly declined. In the three obese subjects restudied after 3- and 24-day fasts an approximate two-fold increase of serum insulin was observed after each acetoacetate infusion. The mean fractional utilization rate of exogenously derived ketone bodies for all 12 subjects after an overnight fast was 2.9% min(-1). In the three obese subjects studied after an overnight, 3 and 24 day fast the mean fractional utilization rates were 2.1%, 1.5%, and 0.6% min(-1), respectively. Ketone body volumes of distribution in the overnight fasted subjected varied from about 18% to 31% of body wt, suggesting that ketone bodies are not homogenously distributed in the body water. In the three obese subjects restudied after 3- and 24-day fasts volumes of distribution remained approximately constant. When total ketone body concentrations in the blood were below 2.0 mmol/liter, there was a linear relationship between ketone body utilization rates and ketone body concentrations; no correlation was found when blood concentrations were higher.

The response of bone to metabolic acidosis in man.

Abstract A metabolic acidosis was produced in obese women by a fasting regimen with no caloric intake. The acidosis was then partially corrected by administering NaHCO 3 while continuing caloric starvation. During acidosis the net negative calcium balance was 156 mg. daily and during the alkali administration this calcium loss was reduced to 51 mg. daily. It was calculated that the anions lost from bone accompanying the calcium loss would combine with 4–8 mMoles H + daily and thus act as a buffer for the extracellular fluid during the acidosis.

Human splanchnic metabolism during diabetic ketoacidosis

Splanchnic exchange rates of glucose, acetoacetate, beta-hydroxybutyrate, lactate, pyruvate, glycerol, alanine, glutamine, glutamate, free fatty acids, and triglycerides were measured in eight patients during moderate to severe diabetic ketoacidosis. Their arterial glucose concentration was 20.68 (9.80-52.79) mumole/liter and tic glucose release was 0.77 (0.09-2.44) mmole/min. Gluconeogenesis accounted for about one-half of net splanchnic glucose release, assuming quantitative conversion of net splanchnic extracted lactate, pyruvate, glycerol, alanine, and alpha-ketoglutarate equivalents to glucose. Net splanchnic free fatty acid extraction was 0.24 (0.09-0.52) mmole/min. There was a positive correlation between free fatty acid uptake and ketone-body release. Net splanchnic acetoacetate release was 0.50 (0.05-0.92) mmole/min and beta-hydroxybutyrate release was 0.35 (-0.16 to 0.84) mmole/min. Total ketone-body release was 0.84 (0.37-1.61) mmole/min. The wide ranges of net splanchnic glucose and ketone-body production rates show the heterogeneous characteristics of the diabetic patient in ketoacidosis. It is concluded that the hyperglycemia and hyperketonemia of diabetic ketoacidosis is due to the lack of reciprocity among rates of hepatic glycogenlysis, gluconeogenesis, and ketogenesis resulting in inappropriate net splanchnic release of glucose and ketone bodies.

Long-term results of femoroinfrapopliteal bypass in diabetic patients with severe ischemia of the lower extremity☆

In patients with severe lower extremity ischemia (ischemic necrosis or pain at rest associated with physical findings of peripheral arterial insufficiency), diabetes mellitus should not deter thorough arteriography and consideration of arterial reconstruction. Infrapopliteal bypass can produce prolonged limb salvage in diabetic patients in lieu of primary amputation.

Substrate, hormone, and temperature responses in males and females to a common breakfast

To evaluate the response to a mixed meal we studied oral temperature, metabolite, and hormonal responses to a common American breakfast containing 11 kcal/kg body weight (carbohydrate 43%, fat 42%, and protein 15%) in 12 normal volunteers (6 males and 6 females). There was a significant rise in oral temperature during the postcibal period. This change in oral temperature did not depend upon food consumption in males but was meal-dependent in females. Food ingestion caused increases in the peripheral circulating concentrations of glucose, lactate, pyruvate, and amino acids and reciprocal decreases in the concentrations of free fatty acids, glycerol, and urea nitrogen. Acetoacetate and beta-hydroxybutyrate decreased during the postcibal period but the changes were not statistically significant. Although peripheral venous serum insulin and plasma glucagon concentrations were indistinguishable between the sexes, males had higher concentrations of plasma triglycerides, plasma amino acids, and serum urea nitrogen. Peripheral venous plasma somatostatin and secretin remained unchanged, but pancreatic polypeptide hormone showed a large biphasic response to the meal. After breakfast the blood glucose concentration tended to be greater in males than in females and this difference was significant at 60 and 120 min postcibal. Furthermore, every female had a 120 min postcibal glucose concentration that was lower than her basal fasting glucose concentration. This suggests that postcibal glucose concentrations should be related to gender in making the diagnosis of carbohydrate intolerance or reactive hypoglycemia.

The Heart in Progressive Muscular Dystrophy

A case of progressive muscular dystrophy with cardiac involvement in a young Negro man is reported. The presenting problem was cardiomegaly and congestive heart failure. It was not until compensation was achieved that the underlying myopathy became apparent. Death was unexpected and presumably sudden. An unusual finding at the postmortem examination was the marked thickening of the endocardium. The literature in regard to the clinical and pathologic manifestations of cardiac involvement in this myopathy is reviewed.