Treatment of type II diabetes.
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Diabetes Mellitus, Type 2↗
Biomedical subjects
M Nattrass
Publications and source records attributed to M Nattrass.
Metabolic and hormonal responses during squash.
The metabolic and hormonal response during squash was observed in eight normal men. Significant increases from resting were found for blood glucose, lactate, pyruvate, alanine and glycerol while total ketone bodies and plasma nonesterified fatty acids rose after play stopped. Insulin and C-peptide decreased significantly and catecholamines, ACTH, prolactin and growth hormone increased.
Adult↗
Metabolic effects of low-dose incremental insulin infusion in diabetic man.
An incremental insulin infusion technique to assess insulin action at physiological circulating levels in diabetic man is described. Insulin was infused during sequential one hour periods at rates of 0.01, 0.05 and 0.10 u/kg/h. Serum free insulin concentrations had reached a plateau by the second 30 minutes of each infusion period. Blood glucose concentrations fell at a similar rate during the two lower rates of insulin infusion, but the fall was significantly greater with the highest insulin infusion. Glucose production and utilisation were measured isotopically using a 3-3H glucose infusion technique. Glucose production was inhibited with the lowest insulin infusion rate and a marked increase in glucose metabolic clearance rate occurred with the highest insulin infusion. Key intermediary metabolites were measured and blood glycerol, total ketone bodies, and plasma non-esterified fatty acids fell with the lowest insulin infusion rate. It is concluded that this technique allows identification of the effect of insulin upon different metabolic processes.
Adult↗
Metabolic rhythms in adolescents with diabetes.
Metabolic rhythms were studied over 24 hours in eight adolescents with insulin dependent diabetes before and two months after attempting to improve diabetic control with home blood glucose monitoring. A significant improvement in blood glucose concentration was observed, although 24 hour mean concentrations remained grossly abnormal. This improvement was accompanied by significant falls in blood glycerol and total ketone bodies concentrations and a significant rise in blood lactate concentration. Without attention to other factors affecting diabetic control, the introduction of home blood glucose monitoring produces only a small improvement in control.
Activity Cycles↗
Metabolic rhythms in adolescents with diabetes during treatment with porcine or human insulin.
Metabolic rhythms were studied over 24 hours in eight adolescent diabetic patients during treatment with porcine insulin and after transfer to human insulin. Despite an increase in dose with human insulin no significant changes were found in fasting blood glucose, 24h mean blood glucose, or glycosylated haemoglobin concentrations. Significantly higher 24h mean blood lactate concentrations and lower total ketone bodies and glycerol concentrations were observed during treatment with human insulin. These findings are consistent with the increase in insulin dose and do not necessarily imply different metabolic responses to species differences in insulin.
Adolescent↗
Erythrocyte insulin receptors following myocardial infarction in non-diabetic subjects.
To determine whether changes in insulin receptors follow acute myocardial infarction, 10 non-diabetic patients were studied on admission to a coronary care unit and 24 h later. Erythrocyte insulin receptors were 86 (50-406) per cell [median (range)] initially and increased significantly to 203 (73-714). Maximum percent specific binding and 50% inhibition of tracer binding did not change significantly. Decreased receptor number after myocardial infarction may contribute to insulin resistance in the acute phase.
Adult↗
Clinical characteristics and aetiological classification of insulin-dependent diabetes in the elderly.
In a prospective study of 195 newly-diagnosed diabetic patients aged 65 years or over, 80 (41.0 per cent) were treated initially by diet, 89 (45.6 per cent) by diet and oral hypoglycaemic agents, and 26 (13.3 per cent) by diet and insulin. Fifteen patients (7.7 per cent) died within a year of diagnosis. Of 26 patients treated with insulin, six died in the first year, 14 were successfully transferred to diet and oral agent treatment and six continued on insulin--two of whom failed to a trial of oral agents, two showed only a temporary response and two received no trial. A further nine patients were taking insulin 12 months after diagnosis because of no response (eight patients) or a transient response (one patient) only to oral agents. Age, percentage ideal body weight, history of acute onset, blood glucose, glycosylated haemoglobin, and random C-peptide concentration at diagnosis did not discriminate between patients requiring insulin at 12 months and those successfully treated without insulin. Patients who were insulin-dependent 12 months after diagnosis had an increased frequency of ketonuria at diagnosis and a previous medical history of endocrine disease. In insulin-dependent patients there was an increased frequency of HLA DR3 but not DR4 and an increased frequency of thyroid microsomal and gastric parietal cell antibodies but not islet cell antibodies. It is concluded that elderly newly-diagnosed diabetic patients who are treated at diagnosis with insulin are not necessarily insulin dependent and can be given a trial of oral agents with safety.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Metabolic response to intravenous infusion of porcine and semi-synthetic human insulin in insulin-dependent diabetic men.
The response of intermediary metabolite concentrations was measured in six insulin-dependent diabetic men during intravenous low-dose incremental insulin infusion. Insulin was infused during consecutive hours at rates of 0.01 u/kg/h, 0.05 u/kg/h and 0.10 u/kg/h. Each patient was studied on two occasions a month apart using either highly purified porcine or semi-synthetic human short-acting insulin. No difference was observed in the changes in blood glucose, lactate, pyruvate, glycerol, alanine, total ketone bodies or plasma non-esterified fatty acids. Thus no difference could be identified in the actions of intravenous porcine and semi-synthetic human insulin on carbohydrate, fat or ketone body metabolism in vivo.
Adult↗
Differences in insulin sensitivity between normal men and women.
An incremental intravenous low-dose insulin infusion has been used to examine differences in insulin sensitivity between normal young men and women. Fasting blood glucose concentration did not differ significantly at the start of the infusion but women had significantly higher plasma insulin and C-peptide concentrations. Similar changes in blood glucose occurred during insulin infusion but insulin concentrations were higher in women. Blood total ketone bodies and alanine were lower in women over the four hours of infusion. Significant differences were found between normal men and women for the effect of insulin upon blood glucose concentration.
Adult↗
Myocardial infarct size and mortality in diabetic patients.
The mortality rate from myocardial infarction is disproportionately high in diabetic patients. One explanation for this may be that diabetic patients incur more extensive myocardial necrosis. This possibility was examined in a three part study. Firstly, peak serum aspartate aminotransferase concentrations of all diabetic and non-diabetic patients admitted with myocardial infarction over a 16 year period were compared retrospectively. Secondly, peak aspartate aminotransferase concentrations in a series of diabetic patients and controls matched by age and sex were examined retrospectively. Thirdly, creatine kinase MB release and electrocardiographic measures of infarct size were investigated prospectively in a case/control study. Although cardiac failure and death were more common in the diabetic groups, there were no significant differences in estimates of infarct size between diabetic and non-diabetic patients in any of the studies. Therefore, the high case fatality rate amongst diabetic patients is not caused by increased myocardial damage. Presumably survival is prejudiced by factors operating before the infarction.
Aspartate Aminotransferases↗
Glucose tolerance test and glycosylated haemoglobin measurement for diagnosis of diabetes mellitus--an assessment of the criteria of the WHO Expert Committee on Diabetes Mellitus 1980.
Fasting glycosylated haemoglobin was analysed in 535 consecutive patients having an oral 75 g glucose tolerance test for diagnostic purposes. A reference range for fasting glycosylated haemoglobin was established from patients with a non-diabetic glucose tolerance test as defined by the World Health Organisation Expert Committee on Diabetes Mellitus. The predictive value of a glycosylated haemoglobin of over 10.0% (mean normal +/- 3 SD) for detecting a diabetic glucose tolerance test was 89% but sensitivity was only 43%. A raised glycosylated haemoglobin is useful for confirming the diagnosis of diabetes mellitus in patients with long-standing hyperglycaemia but glycosylated haemoglobin is within the reference range in many patients with newly developed diabetes or other minor abnormalities of glucose tolerance. The glucose tolerance test must remain the test of choice in these patients.
Adolescent↗
Metabolic effects of bicarbonate in the treatment of diabetic ketoacidosis.
The effect of intravenous bicarbonate on the changes in intermediary metabolites during the initial treatment of diabetic ketoacidosis was examined in 16 patients. The results were compared with the changes seen in 16 patients receiving intravenous saline. Infusion of 150 mmol (mEq) bicarbonate significantly delayed the fall in blood lactate, lactate:pyruvate ratio, and total ketone bodies observed in the saline treated group. No difference in the rate of fall of blood glucose concentration was found. There is no metabolic indication for the use of intravenous bicarbonate in the treatment of diabetic ketoacidosis.
Adolescent↗
Newly diagnosed, insulin-dependent diabetes mellitus in elderly patients.
Over a two-year period 398 out of 1776 new referrals to a diabetic clinic were newly diagnosed diabetic patients aged 65 years and over. Initial treatment of this group was diet--122 (31%), diet plus oral hypoglycaemic agents--232 (58%) and diet plus insulin--41 (10%). Sixteen (39%) of the group treated initially with insulin died within 3.5 years of diagnosis compared with 21% of the 345 patients treated with diet +/- oral hypoglycaemic agents who were followed for this time. Twenty-five patients treated initially with insulin survive but 8 have stopped insulin and are treated with diet +/- oral hypoglycaemic agents, and a further 5 had a period of 6-24 months on oral therapy. Twelve patients have been treated with insulin continuously but of these only 3 are clearly insulin-dependent. These data suggest that true dependence on insulin is uncommon in patients aged 65 years or over at diagnosis.
Aged↗
Effect of intravenous insulin infusion on mortality among diabetic patients after myocardial infarction.
A review of the records of 353 diabetic patients after a myocardial infarction confirmed the high mortality associated with the condition. The influence of improved diabetic control achieved by intravenous insulin was assessed in 64 patients and compared with earlier experience in a diabetic control group. The frequency of the major complications of myocardial infarction was unchanged and the death rate in both groups was identical (33%); even the patients with blood glucose concentrations greater than 20 mmol/l on admission failed to benefit. Thus careful control of blood glucose concentrations after myocardial infarction in diabetic patients fails to improve the outcome of this high risk group.
Aged↗
The effect of diet on intermediary metabolite concentrations in Type 2 (non-insulin-dependent) diabetes mellitus.
The metabolic response to a standard meal was studied in six Type 2 (non-insulin-dependent) diabetic patients at diagnosis and following 4-6 weeks of dietary treatment. The fall in blood glucose concentration following treatment was accompanied by significant reductions in circulating concentrations of lactate, pyruvate, alanine and glycerol. Blood 3-hydroxybutyrate concentrations also fell with treatment.
3-Hydroxybutyric Acid↗
Hormone and metabolite profiles in alcoholic liver disease.
Circulating hormone and metabolite profiles have been studied in ten patients with alcoholic cirrhosis, five patients with alcoholic hepatitis and/or fatty liver, and nine normal controls over a 12-h period of meals and activity. Blood glucose was elevated throughout the day in both cirrhotic and non-cirrhotic alcoholics (mean 12-h glucose; controls 5.38 +/- 0.16 (SEM) mmol/l; cirrhotics 6.98 +/- 0.30 mmol/l, P less than 0.001; non-cirrhotics 7.18 +/- 0.26 mmol/l, P less than 0.001). Non-cirrhotic alcoholics had an exaggerated insulin response to meals, whereas cirrhotic patients had hyperinsulinaemia throughout the day (mean 12-h insulin; controls 16.3 +/- 2.3 mU/l; cirrhotics 35.8 +/- 6.6 mU/l, P less than 0.02). Growth hormone levels were elevated only in patients with cirrhosis (mean 12-h growth hormone, 7.06 +/- 1.35 v. 0.85 +/- 0.17 micrograms/l, P less than 0.001). Serum cortisol was persistently elevated in cirrhotics but only in the evening in non-cirrhotic alcoholics. Lactate and pyruvate responses to meals were exaggerated in non-cirrhotic patients whereas in cirrhotics, levels were persistently raised. Blood glycerol was elevated in all alcoholic patients whereas ketone body levels were normal. Hypertriglyceridaemia was observed only in non-cirrhotic patients. No relationship between the endocrine and metabolic state was observed in either cirrhotic or non-cirrhotic patients.
Adult↗
Use of low-dose insulin infusions in diabetics after myocardial infarction.
Myocardial infarction in diabetics is often accompanied by poor diabetic control. An assessment of a low-dose insulin infusion regimen in 26 diabetic patients after myocardial infarction found this system to be simple, effective, and safe.
Adult↗
The metabolic and hormonal response to acute normoglycaemia in type 1 (insulin-dependent) diabetes: studies with a glucose controlled insulin infusion system (artificial endocrine pancreas).
Twelve insulin deficient Type 1 (insulin-dependent) diabetic subjects were studied over an 11 1/2 h period during both subcutaneous insulin therapy and closed loop insulin delivery, using a glucose controlled insulin system (Biostator) programmed to maintain normoglycaemia. Results were compared with those from 21 age and weight-matched normal subjects. Using the Biostator, normoglycaemia was achieved in all diabetic subjects within 3.5 h and normal profiles maintained thereafter. Blood metabolite and hormone values were evaluated during the subsequent 8 h normoglycaemic period. Subcutaneous therapy resulted in abnormal glucose levels throughout the study period (mean 8 h value 8.3 +/- 0.7 compared with 5.6 +/- 0.3 mmol/l on feedback control and 5.5 +/- 0.1 mmol/l in normal subjects). The mean value of lactate and pyruvate over the final 8 h period was 25% higher in diabetic patients than in normal subjects with no difference between the two insulin treatments (blood lactate: 0.94 +/- 0.04 on subcutaneous insulin, 0.91 +/- 0.04 on feedback control and 0.74 +/- 0.03 mmol/l in control subjects). The pre-prandial peaks of blood glycerol and plasma non-esterified fatty acids were significantly decreased or absent during both feedback control and subcutaneous therapy in comparison with the normal subjects, whereas after the midday and evening meals, total ketone body levels were significantly higher in the diabetic patients. Peripheral serum free insulin levels were two-to fourfold greater in the diabetic than in the normal subjects. There were no significant differences between levels in diabetic patients receiving subcutaneous insulin or on the Biostator. Glucose turnover (1600-1800 h) was normal on feedback control (1.41 +/- 0.20 versus 1.55 +/- 0.18 mg X kg-1 X min-1 in the normal subjects) but was significantly decreased during subcutaneous insulin (1.04 +/- 0.09 mg X kg-1 X min-1). There was, in addition, a decrease in glucose recycling during both subcutaneous insulin therapy and feedback control in the diabetic subjects. These data suggest that although fine control of glucose metabolism both in terms of circulating concentrations and rates of production can be achieved by feedback-control, insulin infusion by the peripheral route is associated with significant metabolic abnormalities, at least in the short term. Longer term studies and examination of portal insulin delivery seem warranted.
Adult↗