Diabetes
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Randomized Controlled Trial Comparative Study Clinical Trial
U.K. prospective diabetes study. II. Reduction in HbA1c with basal insulin supplement, sulfonylurea, or biguanide therapy in maturity-onset diabetes. A multicenter study.
Newly presenting maturity-onset diabetic subjects were put on diet and if, after 3-4 mo, their fasting plasma glucose continued greater than 6 mmol/L, they were randomized to three therapies: (1) continuing diet alone, (2) with additional sulfonylurea, or (3) with additional basal insulin supplement provided by ultralente insulin. Obese patients were also randomized to metformin therapy. The aim was to lower the fasting plasma glucose to less than 6 mmol/L and the degree to which this reduced the hemoglobin A1C (HbA1C) concentration was studied in 195 patients over 1 yr. ⋯ Patients randomized to diet alone had little change in fasting plasma glucose (8.6 +/- 1.8 to 9.3 +/- 2.3 mmol/L) or HbA1C (8.8 +/- 1.7% to 9.1 +/- 1.6%, respectively). Thus, the simple therapeutic aim of trying to reduce the fasting plasma glucose to less than 6 mmol/L is an effective means of reducing the HbA1C to a high-normal level. The HbA1C and fasting plasma glucose concentrations were similarly related for all three therapies (HbA1C [%] = 0.47 X fasting plasma glucose [mmol/L] + 4.7).(ABSTRACT TRUNCATED AT 250 WORDS)
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Comparative Study
Ketone body production and disposal in diabetic ketosis. A comparison with fasting ketosis.
This work compares the metabolism of total ketone bodies in 13 insulin-deprived, type I diabetic subjects and 26 control subjects fasted for 15 h to 23 days, with the two groups showing a similar range of ketone body levels (1-12 mM). Ketone turnover rate was measured using a primed, constant infusion of either 14C-acetoacetate or 14C-beta-hydroxybutyrate, both tracers yielding comparable results. The major conclusions of this study are the following: the kinetics of ketone bodies are comparable in the two groups within the range of concentrations tested. ⋯ The inverse relationship between the metabolic clearance and the plasma levels of ketones, which underlies this process, represents a general characteristic of ketone body metabolism that applies to both types of ketosis. A maximal metabolic disposal rate of about 2.3 mmol/min/1.73 m2 is attained in both groups at concentrations of 10-12 mM, which correspond to the highest ketone body levels encountered during prolonged fasting. Thus, up to these levels, there is no evidence for the existence of a ketone body removal defect specific to diabetes.
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To more fully characterize the alterations in myocardial adrenergic and cholinergic receptors induced by the diabetic state, we investigated the binding characteristics of (--) [3H] dihydroalprenolol to beta adrenergic receptors (bAR), [3H] prazosin to alpha adrenergic receptors (aAR), and [3H] quinuclidinyl-benzilate to muscarinic cholinergic receptors (MCR) in myocardial membranes derived from rats 8 wk after treatment with streptozotocin. We also studied an equal number of animals from three control groups: free-eating nondiabetics, pair-weighted nondiabetics, and streptozotocin-treated animals treated daily with insulin. Diabetic hearts demonstrated 27% fewer bAR (P less than 0.01) and 31% fewer aAR (P less than 0.01) than free-eating controls, without changes in MCR, and without changes in antagonist affinity, agonist affinity, or agonist slope factor (pseudo-Hill coefficient) for any class of receptors. ⋯ The parallel decrease in both bAR and aAR suggests that streptozotocin-induced hypothyroidism is not the primary causative factor of bAR downregulation in this model, since hypothyroidism produces upregulation of aAR. Furthermore, the lack of change in cardiac MCR suggests that the adrenergic receptor alterations are not the result of nonspecific abnormalities of protein synthesis in the diabetic heart. Further studies are required to establish the physiologic significance of these receptor alterations, but these data support the hypothesis that altered adrenergic receptor properties may underlie, at least in part, the chronotropic and inotropic abnormalities of cardiac performance that are associated with the diabetic state.
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To determine the mechanism of hyperchloremic acidosis during recovery from diabetic ketoacidosis (DKA), serial measurements were made in eight patients of serum and urinary electrolytes and organic acids, and of urinary net acid. On admission, the average decrease in serum total CO2 was 17.5 mmol/L, corresponding to the excess anion gap, 18.5 meq/L, and the serum organic acids, 17.1 meq/L. With the treatment, the anion gap and organic acids decreased by 16.1 and 14.7 meq/L, respectively, but the serum CO2 increased only by 8.4 mmol/L; serum electrolyte balance was maintained by increase in chloride concentration. ⋯ Renal loss of bicarbonate precursors during treatment was modest and was exceeded by renal bicarbonate production. The disparity between the increase in serum CO2 and the decrease in organic acids during treatment of DKA may be explained to a large extent by a difference in volume of distribution between bicarbonate and organic anions. The renal loss of ketone anions before admission, however, is ultimately responsible for the persistence of substantial metabolic acidosis.