Pietro Vannini

Lipid Abnormalities in Insulin-dependent Diabetic Patients with Albuminuria

The relationship between serum lipid, lipoprotein, and apolipoprotein levels and abnormalities of renal function has been investigated in 112 insulin-dependent (type I) diabetic patients. They were subdivided into three matched groups according to the amount of albuminuria: group A (albuminuria < 20 μg/min), group B (albuminuria between 20 and 150 μg/min; Albustix negative), and group C (albuminuria > 150 μg/min; Albustix positive). Twenty-one nondiabetic subjects with albuminuria above 150 μg/min but without nephrotic syndrome and/or renal failure and 77 healthy subjects were also studied. Mean total and LDL cholesterol, triglycerides, and apo B were higher, while HDL cholesterol and HDL/LDLcholesterol ratio were lower in group C than in groups A and B; the apo A/apo B ratio was lower in group C than in group A. Differences in apo B and in apo A/apo B ratio were found between groups A and B. No correlation between lipid parameters and amount of albuminuria was observed. Significant differences in lipid concentrations were also found in diabetic patients when compared with nondiabetic subjects with albuminuria and with healthy subjects. The present study confirmed previous reports of lipid disorders in insulin-dependent (type I) diabetes; however, the most important observation was the finding of albuminuria-related differences in lipid parameters in diabetic patients without renal failure. We think that the greater lipid abnormalities observed in diabetic patients with larger amounts of albuminuria might be the consequence both of impairment of glomerular permeability and of the diabetic state.

Insulin-dependent metabolism of branched-chain amino acids in obesity

The effect of euglycemic hyperinsulinism on branched-chain amino acids (BCAA; valine, isoleucine and leucine) was evaluated in five obese subjects and five controls. A continuous intravenous insulin infusion raised plasma insulin to a steady-state level. An artificial endocrine pancrease that infused glucose was used to sustain euglycemia. Basal and steady-state insulin levels were significantly higher in the obese subjects than in the controls. The amount of glucose infused to maintain euglycemia and its ratio to steady-state insulin levels was significantly lower in the obese subjects, suggesting an impaired insulin action on glucose metabolism. Basal BCAA levels were similar in the two groups of subjects. During insulin infusion the decremental areas of BCAA below basal levels were significantly lower in the obese patients (63 +/- 5 nmol/mL X min v 143 +/- 8 nmol/mL X min, P less than 0.001), as was the ratio of the decremental areas of BCAA to the incremental areas of insulin (1.11 +/- 0.05 nmol/microU v 3.30 +/- 0.24 nmol/microU, P less than 0.001). Our data suggest that insulin resistance in obesity reduces hormonal effects on glucose as well as on BCAA metabolism.

Branched-chain amino acids and alanine as indices of the metabolic control in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients

SummaryAlterations in plasma branched-chain amino acids (valine, isoleucine and leucine) and alanine have been described in patients with insulin-dependent diabetes mellitus who have poor metabolic control. To assess the relevance of these abnormalities as indices of metabolic control, we sequentially evaluated plasma amino acids in 14 poorly controlled diabetics (seven Type 1 (insulin-dependent) and seven Type 2 (non-insulin-dependent) patients) until good control was achieved. The sum of branched-chain amino acids in both groups of uncontrolled diabetic patients was significantly increased compared with the values for the same subjects in good metabolic control. No statistically significant differences were present between ketotic and non-ketotic uncontrolled patients. The amelioration of the diabetic state with either insulin treatment or oral hypoglycaemic agents, reduced progressively branched-chain amino acids. The sum of valine, isoleucine and leucine strictly correlated with daily urinary glucose (r=0.73), but less well with fasting blood glucose (r=0.43), nonesterified fatty acids (r=0.46) and glycosylated haemoglobin (r=0.38). Alanine did not show any statistically significant differences at various stages of diabetic control. Branched-chain amino acids, but not alanine, may be used as indices of short-term diabetic control.

Muscle protein breakdown in uncontrolled diabetes as assessed by urinary 3-methylhistidine excretion

SummaryIn an attempt to evaluate muscle protein catabolism in patients with uncontrolled diabetes, urinary excretion of 3-methylhistidine was measured in eight diabetic subjects, during poor control and after achievement of satisfactory control. The results were compared with the excretion values of ten healthy subjects fed a similar amount of meat. In the diabetic patients in poor metabolic control, 3-methylhistidine excretion was significantly increased compared with the healthy subjects, and returned to normal when a satisfactory glycaemic control was achieved. No significant differences were observed between ketonuric and non-ketonuric uncontrolled patients. Improved glycaemic control reduced 3-methylhistidine excretion in both insulin-dependent and non-insulin-dependent diabetes. These results suggest increased protein catabolism causing muscle protein loss and negative nitrogen balance in diabetic patients with poorly controlled disease.

Insulin resistance is the main determinant of impaired glucose tolerance in patients with liver cirrhosis

To clarify the pathogenesis of impaired glucose tolerance in patients with cirrhosis, several factors possibly affecting carbohydrate metabolism were studied in 12 cirrhotic patients with different blood glucose responses to an oral glucose tolerance test. Glucose levels, 120 min after the load, were inversely and significantly related to insulin sensitivity, measured by means of the euglycemic “glucose clamp” technique (r=−0.746). Basal and glucose-induced insulin secretion (insulin and C-peptide levels) only slightly correlated with glucose tolerance, which was not related to functional liver cell mass (galactose elimination), portal-systemic shunting (degree of varices at endoscopy), or maximal glucose-independent insulin secretion (peak C-peptide levels after a glucagon test). Multiple regression analysis identified insulin sensitivity and liver cell mass as the independent variables able to explain most of the variance of 120-min blood glucose (about 84%), and both of them contributed considerably to the regression. While reduced insulin sensitivity is probably the main cause of impaired glucose tolerance, the reduced hepatocellular mass only appears to modulate the degree, and therefore the clinical relevance, of this defect.

Diabetes as pro-infective risk factor in total hip replacement.

SummaryIt is widely accepted that diabetic patients, above all poorly controlled ones, are more susceptible to infection. To verify whether diabetes might be considered a pro-infective risk factor in total hip replacement, 1,042 patients, who from 1969 to 1979 underwent an operation for arthropros thesis of the hip, were studied. The patients were subdivided into two groups according to whether they were diabetic or not. The diabetic patients, though well controlled by diet or by diet plus oral hypoglycemic agents, received insulin for at least two days before surgery. In the early post-operative phase they showed transient worsening of glycemic control rapidly corrected by increased insulin dosage. The patients of both groups were operated in low air exchange operating theaters, by the same staff and using standardized surgical techniques, and all received antibiotic coverage as preventive treatment against infections for a week after surgery. Infection and suppuration occurred in 11% of diabetic patients and only in 2% of non-diabetic patients (p<0.001); in these cases the prostheses were removed after unsuccessful antimicrobial treatment. Our study indicates that diabetes mellitus must be considered a proinfective risk factor in patients who undergo an operation for total hip replacement and suggests that a conservative approach is required in diabetic patients.

Hyperglycemic Effect of Sucrose Ingestion in IDDM Patients Controlled by Artificial Pancreas

The hyperglycemic effect of 28 g sucrose, taken during a mixed meal, was studied in six insulin-dependent diabetes mellitus (IDDM) patients controlled by artificial pancreas. On 2 consecutive days the patients were given, in random order, two Italian meals containing macaroni, bread, meat, vegetables, fruit, olive oil, and an eggnog made with sucrose (meal A) or saccharin (meal B). The two meals were isocaloric and contained equal amounts of carbohydrates. The feedback control on blood glucose continued for 180 min after the meals. Plasma glucose levels and insulin infusion rates delivered by the artificial pancreas after the two test meals did not show any significant differences regarding basal and peak values, peak times, and areas under the curves. A modest amount of sucrose, taken during a mixed meal, does not produce a hyperglycemic effect higher than an equal amount of complex carbohydrates in IDDM patients controlled by artificial pancreas. The same may be expected in well-controlled IDDM patients in conventional therapy because a correlation exists between insulin requirement for conventional therapy and insulin delivered during glucose-controlled insulin infusion.

Long-term effects of eating sucrose on metabolic control of type 1 (insulin-dependent) diabetic outpatients

SummaryThe aim of the study was to investigate the effects of regularly eating a moderate amount of sucrose (30 g/day) in 12 type 1 (insulin-dependent, IDDM) diabetic outpatients in fair blood glucose and lipid control. Two diets, each lasting two month, were compared in a randomized cross-over study. The former was a high-carbohydrate high-fiber diet for diabetic patients with Italian alimentary habits, the latter had the same composition except that 30 g of sucrose replaced 30 g of complex carbohydrates with high glycemic index (bread). The two diets contained equal amounts of carbohydrates, proteins and lipids; the only difference being the contribution of oligosaccharides to total carbodhydrates (22%vs 34%) and cholesterol amount. During the control diet, glycosylated hemoglobin was substantially unchanged in both control and sucrose diet periods (control diet: 6.91±0.29 (SE)vs 6.80±0.25%; sucrose diet: 6.75±0.31vs 6.91±0.36%). This was true also for fructosamine (control diet: 3.92±0.21vs 3.76±0.18%; sucrose diet: 3.50±0.14vs 3.64±0.20 mmol/l). Circulating blood lipid levels, body weight and daily insulin dose did not show any significant variations during the study. Moderate amounts of sucrose may be allowed to IDDM patients with Italian alimentary habits without worsening diabetic control.

Effects of Mixing Short- and Intermediate-Acting Insulins on Absorption Course and Biologic Effect of Short-Acting Preparation

The effects of mixing short-and intermediate-acting insulins (Actrapid MC and Monotard MC) were studied in seven diabetic patients. On different days, 0.16 IU/kg of Actrapid and 0.24 IU/kg of Monotard were administered to each subject in separate injections and combined in the same syringe. Free-insulin curves and the biologic effect of insulin, assessed by the glucose-clamp technique, were compared. The absorption rate of regular insulin was higher when injected separately from the intermediate-acting preparation: the incremental areas of free insulin above basal levels, up to 90 min after the administration of the hormone, were 32 ± 5 vs. 21 ± 3μU · ml−l · min−1 (P < .02). In the same period, glucose infused to sustain glycemia showed no significant differences (2.8 ± 0.4 vs. 2.4 ± 0.3 mg · kg−1 min−1 after the administration of insulin in separate and combined injection, respectively). The difference in insulin profiles is not translated into a significant difference in glucose requirement. This might be a consequence of a flattening of the insulin dose-response curve due to insulin resistance of diabetic subjects. The slight delay in insulin action of Actrapid when mixed with Monotard is probably irrelevant in clinical practice.

Enhanced Pressor Responsiveness to Norepinephrine in Type II Diabetes: Effect of ACE inhibition

OBJECTIVE To evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on the pressor responsiveness to norepinephrine in type II diabetes. RESEARCH DESIGN AND METHODS Eight normotensive subjects, eight mild-to-moderate hypertensive type II diabetic patients, and eight nondiabetic patients with essential hypertension were studied before and after 4 weeks of being administered enalapril. The pressor response to norepinephrine was assessed by infusing the hormone in an antecubital vein at incremental doses of 30 ng·kg−1 · min−1 for periods of 5 min until reaching an increase of 20 ± 2 mmHg in mean arterial pressure (MAP) measured by an automatic device at 1-min intervals. An effective dosage of norepinephrine that increased MAP by 20 mmHg (EDNE 20) was thereafter calculated. Before and during the last minute of norepinephrine infusion at maximum dosage, a venous blood sample was drawn to determine plasma renin activity (PRA), aldosterone, and norepinephrine levels. RESULTS In the three groups of patients, blood pressure and aldosterone were reduced while PRA was raised following ACE inhibition. Basal and maximum postinfusion levels of norepinephrine were not modified by enalapril. The EDNE 20 was basally lower in diabetic patients and remained unchanged after ACE inhibition, contrary to that observed in nondiabetic patients with essential hypertension. CONCLUSIONS Both normotensive and hypertensive type II diabetic patients have an increased pressor responsiveness to norepinephrine that is not modified by therapeutic doses of enalapril, contrary to what is observed in nondiabetic patients with essential hypertension.