Acidosis: The Prime Determinant of Depressed Sensorium in Diabetic Ketoacidosis

OBJECTIVE — The etiology of altered sensorium in diabetic ketoacidosis (DKA) remains unclear. Therefore, we sought to determine the origin of depressed consciousness in DKA. RESEARCH DESIGN AND METHODS — We analyzed retrospectively clinical and biochemical data of DKA patients admitted in a community teaching hospital. RESULTS — We recorded 216 cases, 21 % of which occurred in subjects with type 2 diabetes. Mean serum osmolality and pH were 304 31.6 mOsm/kg and 7.14 0.15, respectively. Acidosis emerged as the prime determinant of altered sensorium, but hyperosmolarity played a synergistic role in patients with severe acidosis to precipitate depressed sensorium (odds ratio 2.87). Combination of severe acidosis and hyperosmolarity predicted altered consciousness with 61 % sensitivity and 87 % specificity. Mortality occurred in 0.9 % of the cases. CONCLUSIONS — Acidosis was independently associated with altered sensorium, but hy-perosmolarity and serum “ketone ” levels were not. Combination of hyperosmolarity and acidosis predicted altered sensorium with good sensitivity and specificity. Diabetes Care 33:1837–1839, 2010 D iabetic ketoacidosis (DKA) is fre-quently associated with alteredmental status, which is correlated with the severity of the disease and prog-nosis (1). However, the etiology of de-pressed sensorium in DKA remains uncertain and controversial (2,3). Puta-tive factors in the pathogenesis of diabetic ketoacidotic coma include cerebral hypo-perfusion due to circulatory collapse and cerebral thrombosis (4), reduced cerebral glucose and oxygen utilization (1,5), aci-dosis (6,7), hyperosmolarity (8,9), and direct toxic effect of ketone bodies (2). Cerebral edema remains an important precipitant of altered consciousness in DKA, especially in children. Different studies have yielded con-flicting results regarding the role of these etiologic factors in the pathogenesis of al-tered mentation in patients with DKA. Hence, the origin of clouded sensorium in DKA remains to be fully elucidated. We undertook to study the etiology of de-pressed consciousness in patients admit-ted with DKA at the Regional Medica

Is a Priming Dose of Insulin Necessary in a Low-Dose Insulin Protocol for the Treatment of Diabetic Ketoacidosis?

OBJECTIVE—The purpose of this study was to assess the efficacy of an insulin priming dose with a continuous insulin infusion versus two continuous infusions without a priming dose

TCF7L2 Polymorphism, Weight Loss and Proinsulin∶Insulin Ratio in the Diabetes Prevention Program

Aims: TCF7L2 variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion. Here we sought to test whether these effects were apparent in high-risk individuals and modify treatment responses. Methods: We examined the potential role of the TCF7L2 rs7903146 variant in predicting resistance to weight loss or a lack of improvement of proinsulin processing during 2.5-years of follow-up participants (N = 2,994) from the Diabetes Prevention Program (DPP), a randomized controlled trial designed to prevent or delay diabetes in high-risk adults. Results: We observed no difference in the degree of weight loss by rs7903146 genotypes. However, the T allele (conferring higher risk of diabetes) at rs7903146 was associated with higher fasting proinsulin at baseline (P, 0.001), higher baseline proinsulin: insulin ratio (p<0.0001) and increased proinsulin: insulin ratio over a median of 2.5 years of follow-up (P = 0.003). Effects were comparable across treatment arms. Conclusions: The combination of a lack of impact of the TCF7L2 genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin: insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production

Actos Now for the prevention of diabetes (ACT NOW) study

Abstract Background Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS®) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial. Methods/Design 602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140–199 mg/dl). In addition, IGT subjects were required to have FPG = 95–125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2–3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated. Primary endpoint is conversion of IGT to T2DM based upon FPG ≥ 126 or 2-hour PG ≥ 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance. Conclusion ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM. Trial Registration clinical trials.gov identifier: NCT0022096