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Seventy-eight critically ill patients who died while on the neurosurgical service were studied retrospectively to establish the prevalence of nonketotic hyperglycemic hyperosmolar coma (NHHC). All the patients had been comatose before death, and all underwent necropsy. Criteria for the diagnosis of NHHC included moderate-to-severe hyperglycemia with glucosuria, absence of significant acetonuria, hyperosmolarity with dehydration, and neurological dysfunction. This study revealed seven cases of unequivocal NHHC (9%), and six of hyperosmolarity but with incomplete records. Five of the seven confirmed cases of NHHC demonstrated no evidence of cerebral edema transtentorial herniation, or brain-stem damage, and showed central nervous system (CNS) lesions compatible with survival. Fatal complications of this syndrome, such as acute renal failure, terminal arrhythmias, and vascular accidents, both cerebral and systemic, were common in this series. The mechanism of coma in NHHC is believed related to shifts of free water from the cerebral extravascular space to the hypertonic intravascular space, with subsequent intracellular dehydration, accumulation of metabolic products of glucose, and brain shrinkage. It is uncertain whether injury to specific areas in the CNS is a predisposing factor to the development of NHHC. Factors documented to be significant in its development include nonspecific stress to primary illnesses, hyperosmolar tube feedings, dehydration, diabetes and mannitol, Dilantin, or steroid administration.
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PMID:Nonketotic hyperglycemic hyperosmolar coma. Report of neurosurgical cases with a review of mechanisms and treatment. 125 32

A protein-sparing modified fast (PSMF), which is a total fast modified by the intake of 1.2-1.4 gm. protein per kilogram ideal body weight (IBW), fluids ad libitum, and vitamin and mineral supplementation, allows effective control of carbohydrate metabolism and hunger. It reduces serum glucose and insulin concentrations in obese diabetic patients and increases free fatty acid and ketone body concentrations; ketonuria appears within 24-72 hours. When this fast was applied to seven obese adult-onset diabetics who were receiving 30-100 units of insulin per day, insulin could be discontinued after 0-19 days (mean, 6.5). In the three patients who had extensive nitrogen-balance studies, balance could be maintained chronically by 1.3 gm. protein per kilogram IBW, despite the gross caloric inadequacy of the diet. The PSMF was tolerated well in an outpatient setting after the initial insulin-withdrawal phase had occurred in the hospital. Significant improvements in blood pressure, lipid abnormalities, parameters of carbohydrate metabolism, and cardiorespiratory, symptoms were associated with weight loss and/or the PSMF. For diabetics with some endogenous insulin reserve, the PSMF offers significant advantages for weight reduction, including preservation of lean body mass (as reflected in nitrogen balance) and withdrawal of exogenous insulin.
Diabetes 1976 Jun
PMID:Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing modified fast. 127 1

Intraperitoneal inoculation with NDK25, a variant of Encephalomyocarditis (EMC) virus which has been newly cloned from the M variant of EMC virus (EMC-M), caused DBA/2 mice to develop noninsulin-dependent diabetes mellitus. The NDK25-infected mice demonstrated abnormal glucose tolerance from 1 to 3 weeks after inoculation. The infection resulted in mild insulitis and the destruction of pancreatic beta cells at 1 week after inoculation and led to a significant reduction in the insulin content of the pancreas, but there was no ketonuria. The insulin content of the pancreas was recovered considerably from 15 +/- 3 at 1 week to 95 +/- 16 micrograms/g pancreas at 12 weeks, although the latter value was still significantly lower than that of the control mice (P < 0.05). Under microscopy, mild and partial infiltration of mononuclear cells was observed in about half the pancreatic islets only 1 week after inoculation, and then disappeared. Thus, we believe we have established a new model of noninsulin-dependent diabetes mellitus using the NDK25 variant of EMC virus.
Diabetes Res 1992
PMID:A new animal model of non-insulin-dependent diabetes mellitus induced by the NDK25 variant of encephalomyocarditis virus. 134 4

Diabetic ketoacidosis remains a significant cause of death in cases of insulin-dependent diabetes mellitus (IDDM). Among patients hospitalised for diabetic ketoacidosis, the death rate is 5-10 per cent, cardiovascular disease, infection, and ARDS (adult respiratory distress syndrome) being major contributory factors, whereas the degree of acidosis does not differ from that among survivors. Ketoacidosis is a major determinant of the two-fold higher mortality among the youngest age-groups of IDDM patients. The age-specific incidence of ketoacidosis among patients under 20 years of age is several time higher than that among patients over 50. Intensified insulin treatment, using multiple injections or insulin pumps, probably results in an increased risk of insulin deficiency owing to the smaller insulin depots. Thus, there is a need of intensified testing for ketonuria and improved education of patients, physicians and other health care personnel, in order to promote the prevention or rapid, effective treatment of diabetic ketoacidosis.
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PMID:[Diabetic coma--an unnecessary death]. 140 26

The French incidence study has registered all new cases of Type 1 diabetic children under 20 years of age, from a population of 2.32 million, in an exhaustive and prospective manner. Three hundred and forty cases were identified between 1 January 1988 and 31 December 1989, yielding a mean annual incidence rate 7.3 per 10(5). The lowest rate was observed in the youngest age group (0-4 yr: 4.1 per 10(5)) and the highest around pubertal development (10-14 yr: 11.5 per 10(5)). Details of the previous personal and family history, and the clinical and biological pictures of the disease at diagnosis were recorded. Almost 8 per cent of the children had a first-degree relative with Type 1 diabetes. Polyuria, weight loss, fatigue and abdominal pain were the most frequently reported symptoms, which were of median duration 4.4 months. Mean weight loss before diagnosis was 9.4 +/- 6.8 (+/- SD)% of body weight and was not significantly related to age. Ketonuria was detected in 83.8 per cent and acidosis (total CO2 less than or equal to 18 mmol l-1, if measured) in 48 per cent of the cases. Ketonuria and acidosis were significantly more frequent in the younger age group than in the rest of the group (p less than 0.001).
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PMID:Clinical and laboratory features of type 1 diabetic children at the time of diagnosis. 157 13

Dichloroacetate (DCA) represents a potentially novel class of oral antidiabetic agents that reduce blood glucose and lipids without stimulating insulin secretion. DCA reduces blood glucose by inhibiting hepatic glucose synthesis and stimulating glucose clearance and use by peripheral tissues. A major site of action of the drug is pyruvate dehydrogenase (PDH), the rate-limiting enzyme of aerobic glucose oxidation. Stimulation of PDH by DCA increases peripheral oxidation of alanine and lactate, thereby interrupting the Cori and alanine cycles and reducing the availability of three-carbon precursors for gluconeogenesis. In experimental models of ketosis, DCA reduces ketonemia and ketonuria while significantly lowering blood glucose. DCA inhibits hepatic triglyceride and cholesterol biosynthesis. Short-term studies in patients with non-insulin-dependent diabetes have demonstrated a capacity of the drug to markedly reduce circulating a very-low-density lipoprotein cholesterol and triglyceride concentrations. In genetic models of insulin-dependent diabetes, oral administration of DCA significantly reduces insulin requirements and blood levels of glucose and triglycerides. Several derivatives of DCA have been synthesized and found to have biological activity in animals. Further work is required to determine whether DCA and its analogues may be safe and effective agents for chronic treatment of the carbohydrate and lipid abnormalities of human diabetes.
Diabetes Care 1992 Jun
PMID:Dichloroacetate. 160 Aug 37

Although hypocaloric diets have been advocated for the management of the obese gravida and the obese mother with gestational diabetes, there is no general agreement on how severely calories should be restricted or on how this therapeutic approach compares with insulin therapy. The lack of consensus is in part because of the lack of studies comparing insulin management with the effects of different degrees of hypocaloric feeding and its effects on metabolism and glycemic status. We review the effects of 50 and 33% calorie restriction on glycemic status and intermediary fuel status in obese gestational diabetic subjects and compare the results with the administration of 20 U NPH and 10 U regular insulin every morning, a therapy of proven value in reducing macrosomia in gestational diabetes. When the two calorie-restriction regimens were compared after a 9-h overnight fast, glycemic status improved 10-20% on both. Ketonuria increased about twofold with 50% calorie restriction, but on average no increase in ketonuria was seen on the 33% calorie-restriction regimen. Both calorie-restriction programs led to a reduction in levels of plasma triglyceride, a correlate of infant birth weight. In contrast, the insulin regimen diminished ketonuria, but glycemic status improved little, and plasma triglyceride concentrations did not decline. Although more studies are needed to confirm these trends, the beneficial effect of 33% calorie restriction, which occurred without marked ketonuria, is consistent with previous studies in gestational diabetes. In addition, the simultaneous improvements observed in plasma glucose and triglyceride concentrations suggest that moderate calorie restriction may be valuable in preventing macrosomia in the offspring of the obese subject with gestational diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Dec
PMID:Metabolic effects of hypocaloric diets in management of gestational diabetes. 174 51

907 consecutive patients, (456 Asian and 451 Caucasian) were assessed, employing a similar methodology to the multi-centre WHO study. The Asians were older at diagnosis (46.5 years compared with 40.6 years, P less than 0.01); they had a shorter duration of diabetes (6.3 years versus 11.4 years, P less than 0.1), a higher rate of diabetes in the first degree relatives (29.5% compared with 16%, P less than 0.1), less ketonuria at presentation (85.3% compared with 47.8%, P less than 0.1), and fewer were treated with insulin (31.4% compared with 68.7%). Comparing the prevalence of complications between Asians and Caucasians, the ischaemic heart disease rate was similar; peripheral vascular disease was less (3.7% Asian, 9.3% Caucasian, P less than 0.05); retinopathy was less (11.6% Asian, 32.3% Caucasian, P less than 0.01) but renal disease was more (22.3% Asian, 12.6% Caucasian, P less than 0.01). After adjusting for age, sex, duration of diabetes, age at diagnosis, hypertension, smoking and treatment with or without insulin, these differences remained significant. Multivariate logistic regression failed to reveal a significant contribution due to any of the above variables, or due to body mass index (BMI), haemoglobin A (HbA1), or physical activity in the prevalence of complications in Asians compared with Caucasians. Marked heterogeneity in the complications of diabetes in the two ethnic groups studied was found, but must be confirmed from population-based studies.
Diabetes Res Clin Pract 1991 Dec
PMID:A comparison of the clinical features and vascular complications of diabetes between migrant Asians and Caucasians in Leicester, U.K. 177 13

It has been suggested that screening all patients with diabetes diagnosed in later life for islet cell antibodies (ICA) would help predict insulin dependence. We have surveyed the case notes of 55 patients (22 male; ages 37-88 years) who were found to be ICA positive over a 9-year screening period to assess what contribution knowledge of ICA status made to their management. Forty-two patients had been put on insulin (half within 6 months of diagnosis and the rest after up to 6 years). Of the 13 patients not on insulin, six were on diet alone and seven on oral hypoglycaemic agents after a median follow-up of 3 years. In 37 of the 42 patients, insulin treatment was started for clinical rather than immunological reasons (diabetic ketoacidosis, ketonuria, weight loss and/or severe symptoms). Five patients were started on insulin because of ICA status when there was no compelling reason on clinical grounds. Knowledge that seven non-insulin-treated patients were ICA positive made doctors reluctant to discharge them from clinic. The data suggest that routine ICA estimation in this age group is unnecessary, as the decision to treat with insulin is best made on clinical grounds, and ICA estimation can lead to unwarranted insulin treatment, or anxiety in patients and doctors who are aware of a positive result.
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PMID:Does knowledge of islet cell antibody status help in managing diabetes presenting in middle and old age? 182 49

Geographic/population variation in the prevalence of diabetic nephropathy is well recognised. In a study of 'native' Indians, we screened 102 non-proteinuric diabetes mellitus patients (64 NIDDM, 38 IDDM; mean age and diabetic duration 48.7 and 6.5 years, 21.6 and 6.2 years, respectively) with blood pressure less than or equal to 170/105 and without congestive heart failure, ketonuria or urinary tract infection, for the presence of microalbuminuria (albumin excretion rate greater than 20 micrograms/min). Fifty-six patients (34 NIDDM, 22 IDDM) also underwent detailed fundus examination. Seventeen NIDDM (26.6%) and 3 IDDM (7.9%) patients had microalbuminuria. Glycated hemoglobin was significantly higher in microalbuminurics in the NIDDM group (P less than 0.05). Diabetic retinopathy tended to occur more frequently in microalbuminurics (NIDDM and IDDM).
Diabetes Res Clin Pract 1991 May
PMID:The prevalence of microalbuminuria in diabetes: a study from north India. 187 3


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