Delayed diagnosis in non-insulin dependent diabetes mellitus.
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Diabetes Mellitus, Type 2↗
Biomedical subjects
B M Singh
Publications and source records attributed to B M Singh.
Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion.
Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 +/- 11.5 v 22.1 +/- 2.2 kg.m-2; mean +/- SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 +/- 3.8 v 2.4 +/- 3.0 mU.L-1, P less than .001) and remained elevated throughout infusion (F = 492, P less than .001), as did C-peptide (F = 22.7, P less than .001). Metabolic clearance rate for insulin (MCRI) at the highest infusion rate was similar (1,048 +/- 425 v 1,018 +/- 357 mL.m-2.min-1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 +/- 108 v 444 +/- 68 mumol.m-2.min-1, P less than .01), as was the basal metabolic clearance rate for glucose (MCRG, 77 +/- 26 v 108 +/- 31 mL.m-2.min-1, P less than .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 +/- 0.5 v 1.9 +/- 0.5 mmol.L-1, P less than .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL.m-2.min-1/mU.L-1, P less than .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were elevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Metabolic effects of monomeric insulin analogues of different receptor affinity.
The effects of two monomeric insulin analogues of differing receptor affinities (human insulin = 100%) B9Asp-B27Glu-insulin (18%) and B10Asp-insulin (327%) were each compared with human insulin in two groups of 10 normal men when infused at equimolar low doses (1.0 and 2.0 pmol kg-1 min-1). The metabolic clearance rate under steady state conditions was highest for the analogue with the highest receptor affinity, 26.8 +/- 0.8 (+/- SE) vs 19.8 +/- 0.7 ml kg-1 min-1 for insulin (p less than 0.001), and lowest for the analogue with the lowest receptor affinity, 13.3 +/- 0.8 vs 25.1 +/- 2.0 ml kg-1 min-1 for insulin (p less than 0.001). The apparent plasma half-life was prolonged for the low affinity analogue compared with human insulin (12.6 +/- 0.6 vs 1.9 +/- 0.2 min, p less than 0.001), and significantly shorter for the higher affinity analogue (1.6 +/- 0.1 vs 3.1 +/- 0.4 min, p less than 0.05). The three insulins gave similar falls in blood glucose, non-esterified fatty acids, glycerol, and total ketone bodies over the infusion period. Thirty minutes after the end of the infusion, the rise in blood glucose for the low affinity analogue was significantly less than for human insulin (0.5 +/- 0.2 vs 0.9 +/- 0.1 mmol l-1, p less than 0.05). Despite different receptor affinities, these analogues have similar in vivo effects in normal men, but the time-course of their actions may differ when they are infused intravenously.
Adult↗
Prevalence of haemochromatosis amongst patients with diabetes mellitus.
Four hundred and six white caucasian patients with diabetes mellitus (243 male, mean age 54 +/- 16 (SD) years) were screened for haemochromatosis. Four patients had a fasting transferrin saturation > 62% and all were HLA A3 positive. Two were probable homozygotes for haemochromatosis and two heterozygotes. Homozygote haemochromatosis prevalence in this diabetic population was therefore 2/406 (0.0049) which is identical to that reported in the general population. These findings do not support a genetic relationship between the two conditions.
Adult↗
Basal intermediary metabolism in impaired glucose tolerance and morbid obesity.
The effects of impaired glucose tolerance and obesity, in isolation and in combination, on basal (postabsorptive) intermediary metabolism were examined in four groups of subjects (n = 10 for each) matched for age and gender: Group 1: Non-obese healthy controls with normal glucose tolerance (75 g); Group 2: Non-obese subjects with impaired glucose tolerance; Group 3: Morbidly obese subjects with normal glucose tolerance; Group 4: Morbidly obese subjects with impaired glucose tolerance. While there was no significant difference in fasting blood glucose concentrations between the four groups plasma immuno-reactive insulin concentrations were elevated (p < 0.01 or less) in the obese subjects relative to the non-obese subjects within each category of glucose tolerance. Basal immunoreactive insulin concentrations in non-obese subjects with impaired glucose tolerance were also elevated (p < 0.01) relative to the non-obese healthy controls. Concentrations of glycerol (p < 0.01), non-esterified fatty acids (p < 0.01), and total ketone bodies (p < 0.001) were significantly higher in the obese/normal glucose tolerance and obese/impaired glucose tolerance groups relative to their matched non-obese counterparts. Compared with the subjects with normal glucose tolerance, only lactate (p < 0.05) and pyruvate (p < 0.05) concentrations were elevated in the non-obese/impaired glucose tolerance and obese/impaired glucose tolerance groups, respectively. In conclusion, in addition to fasting hyperinsulinaemia the regulation of lipolysis and ketone body metabolism is abnormal in the basal state in morbid obesity. By contrast, despite normal fasting blood glucose concentrations, impaired glucose tolerance is associated with disturbances of other aspects of basal carbohydrate metabolism.
Adult↗
Detection of glibenclamide in oral insulin capsules.
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Administration, Oral↗
Public awareness of the symptoms of diabetes mellitus.
A cross-sectional survey by standard questionnaire was conducted to determine the public's knowledge (n = 480) of diabetes and diabetes symptoms. Four hundred and sixty-two (96%) subjects had heard of diabetes, 350 (73%) could give a rudimentary definition of diabetes, but 231 (48%) were unable to name any symptom and only 20 (4%) knew of thirst and polyuria in combination. The public's knowledge of diabetes symptoms is poor. This may possibly contribute to delayed presentation of Type 2 diabetes.
Adult↗
Impaired glucose tolerance in obesity is associated with insensitivity to insulin in multiple aspects of metabolism as assessed by a low dose incremental insulin infusion technique.
To determine whether Impaired Glucose Tolerance gives rise to additional defects in insulin action in lipid and ketone metabolism, thirty-two obese subjects were studied by low-dose incremental insulin infusion. Sixteen had Impaired Glucose Tolerance and 16 had normal glucose tolerance. Body mass index was 36.9-80.9 kg m-2 and was similar in each group. In patients with Impaired Glucose Tolerance, plasma insulin was higher in the fasted state (logarithmic mean 14.5 (9.8-21.6) (-SD(-)+SD) vs 9.6 (6.4-14.5) mU l-1, p less than 0.01) and during the infusion (p less than 0.001). The metabolic clearance rate for insulin at the highest infusion rate was lower (14.2 +/- 0.8 (+/- SE) vs 18.9 +/- 2.1 ml kg-1 min-1, p less than 0.05) in these subjects. Basal hepatic glucose production was higher in subjects with Impaired Glucose Tolerance (6.3 +/- 0.4 vs 4.5 +/- 0.6 mol kg-1 min-1, p less than 0.02) and remained elevated during infusion (p less than 0.01). Glucose disposal per unit circulating insulin at the maximal infusion rate was approximately half in subjects with Impaired Glucose Tolerance (0.022 +/- 0.010 vs 0.047 +/- 0.017 ml kg-1 min-1 mU-1 l, p less than 0.01). When simultaneous insulin and metabolite concentrations during the infusion are plotted as dose-response relationships, a difference in relative sensitivity to insulin in Impaired Glucose Tolerance over subjects with normal glucose tolerance is suggested for non-esterified fatty acids 0.72 (95% CI 0.62-0.84) and glycerol 1.85 (1.37-2.49).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
A community-based study of diabetes-related skills and knowledge in elderly people with insulin-requiring diabetes.
An open cross-sectional study of elderly (age greater than 65 yr) patients with insulin-requiring diabetes mellitus (n = 57) was undertaken to audit safety of self-management. Levels of knowledge and management skills of hypoglycaemia, hyperglycaemia, and foot care were determined. The prevalence of hypoglycaemia, visual impairment, and at-risk feet and the ability to perform practical procedures (insulin injection and self-monitoring) were assessed. Drawing up insulin and self-injection was correct in 84% and 76% of patients, but 53% of self-monitored urine or blood tests were performed incorrectly. Twenty-six per cent experienced hypoglycaemia at least monthly and 25% had been seen at the hospital with hypoglycaemia in the last year. Eighteen per cent did not know what action to take with hypoglycaemia. Forty-six per cent did not know any hyperglycaemic symptoms or signs. Prompted with symptoms, 35% still did not know what to do and 21% would take inappropriate action when self-monitored tests read high. Fifty-one per cent had impaired vision, 61% peripheral neuropathy and 24% peripheral vascular disease, with the result that 78% had at-risk feet. Fifteen percent inspected or washed their feet infrequently, 40% walked barefoot occasionally, and 47% would take potentially dangerous action in the event of foot injury. This study demonstrates serious deficiencies in the basic education and management skills in our elderly insulin-requiring diabetic population that could result in morbidity and mortality. Greater effort and vigilance by health care professionals must be directed towards this group.
Aged↗
Impaired glucose tolerance is characterized by multiple abnormalities in the regulation of intermediary metabolism.
The responses of circulating intermediary metabolites to a low-dose sequential insulin infusion (basal, 0.005, 0.01, and 0.05 U kg-1 h-1) were assessed in eight non-obese men with Impaired Glucose Tolerance (IGT), and in eight healthy control subjects with normal glucose tolerance matched for age, gender, and body mass index. Fasting hyperinsulinaemia was observed in the subjects with IGT (7.4 +/- 1.0 vs 2.9 +/- 0.3 mU I-1, p less than 0.001). While there was no significant difference (p greater than 0.1) in fasting venous glucose levels between the groups, fasting concentrations of lactate (p less than 0.02), alanine (p less than 0.01), and glycerol (p less than 0.05) were significantly elevated in the subjects with IGT. During the incremental insulin infusion, overall concentrations of glucose (p less than 0.05), lactate (p less than 0.05), alanine (p less than 0.05), glycerol (p less than 0.05), immunoreactive insulin (p less than 0.001), and C-peptide (p less than 0.01) were significantly higher in the subjects with IGT. Linear dose-response relationships (p less than 0.005) for circulating immunoreactive insulin (log) vs metabolite concentrations were demonstrated by analysis of variance for glucose, non-esterified fatty acids (NEFA), glycerol, and total ketone bodies. For glucose, glycerol, and NEFA, group dose-response regression lines for the subjects with IGT were displaced significantly to the right (p less than 0.001 for each) of those for the normal control subjects, implying insulin insensitivity. In addition to the recognized defect in glucose homeostasis, these results indicate impaired regulation of multiple aspects of intermediary metabolism including lipolysis in IGT.
Alanine↗
Effect of obesity on circulating intermediary metabolite concentrations in the absence of impaired glucose tolerance.
The published literature on the influence of obesity on intermediary metabolite concentrations does not adequately address the potential confounding effects of the increased prevalence of impaired glucose tolerance in obese subjects. In order to remove this, we studied 109 subjects with proven normal glucose tolerance ranging from underweight to grossly obese (range 15.3-80.9 body mass index). All had blood intermediary metabolites, plasma insulin and C-peptide measured after an overnight fast. Thirty-six (18 from each end of the range of body mass index) received a 3-hour oral glucose tolerance test for metabolites and insulin. Fasting plasma insulin was highly significantly associated with body mass index (r = 0.72; P less than 0.001). Concentrations of lipid intermediaries were better associated with body mass index than with fasting plasma insulin: non-esterified fatty acids (r = 0.36; P less than 0.001), glycerol (r = 0.47; P less than 0.001) and ketone bodies (r = 0.45; P less than 0.001). Fasting concentrations of carbohydrate intermediaries were, however, better correlated with fasting plasma insulin: lactate (r = 0.29; P less than 0.01), pyruvate (r = 0.24; P less than 0.01) and alanine (r = 0.36; P less than 0.001). Glucose concentrations were associated with both to a similar degree (r = 0.33, r = 0.32, respectively; P less than 0.001). After oral glucose, exaggerated rises in plasma insulin and blood glucose were observed in obese subjects but a lesser rise was seen for lactate. Non-esterified fatty acids and ketones, although having higher fasting concentrations in obese subjects, fell to similar concentrations in the two groups after glucose whereas blood glycerol did not fall so far in the obese subjects. The results suggest, even if those subjects with impaired glucose tolerance are excluded, insensitivity to insulin in several aspects of intermediary metabolism in obesity the degree of which may vary in different metabolic pathways or tissues.
Adult↗
Metabolic abnormalities in obese patients with impaired glucose tolerance.
It is not clear whether the glucose tolerance test diagnosis of Impaired Glucose Tolerance introduced in the recent revisions of diagnostic criteria is associated with abnormalities of intermediary metabolism other than glucose. Intermediary metabolite concentrations have therefore been studied fasting and in response to oral glucose in 35 patients referred with morbid obesity accompanied by either normal glucose tolerance (18 patients) or Impaired Glucose Tolerance (17 patients). When fasting obese patients with Impaired Glucose Tolerance had significantly higher blood total ketone body concentrations, 0.24 (0.19-0.30) vs 0.14 (0.12-0.16) mmol l-1 (antilog of mean-SE to mean + SE) (p less than 0.05), and lower blood glycerol concentrations, 0.14 +/- 0.01 vs 0.18 +/- 0.01 mmol l-1 (mean +/- SE) (p less than 0.05), than obese patients with normal glucose tolerance. There were no significant differences in fasting insulin, 16 (15-18) vs 14 (12-15) mU l-1, or glucose levels, 5.3 +/- 0.2 vs 5.1 +/- 0.2 mmol l-1. After oral glucose there was an exaggerated rise in glucose, insulin, lactate, and pyruvate in patients with Impaired Glucose Tolerance.
Adult↗
Changing sex ratio in diabetic ketoacidosis.
An annual audit of diabetic ketoacidosis and hyperosmolar non-ketotic state was made in one hospital from 1971 to 1988. There were 846 episodes of ketoacidosis and 126 episodes of hyperosmolar state. A relative fall occurred in the number of episodes of ketoacidosis compared with hyperosmolar state over this time (p less than 0.05), and there was a change of female:male ratio for episodes of ketoacidosis occurring in established diabetes from 2.79 to 1.59 (p less than 0.01). In contrast the female:male ratio remained unchanged (mean 1.16) for episodes of hyperosmolar state and remained less than 1.0 for all episodes of ketoacidosis in previously undiagnosed diabetes mellitus. Among patients who suffered recurrent ketoacidosis there was a reduction in the number of episodes occurring in female patients and an increase in the number of episodes occurring in male patients in each successive 6-year period with consequent change in female:male ratio for this subgroup from 7.33 to 4.75 to 1.12 (p less than 0.001).
Adolescent↗
Use of combined oral contraceptive preparations alters the insulin sensitivity of fatty acid and ketone metabolism.
Eight women taking low-dose-oestrogen combined oral contraceptive preparations were compared to eight women in the luteal phase of the menstrual cycle during hourly incremental insulin infusions of 0 (basal), 0.005, 0.01 and 0.05 U/kg/h short-acting insulin. Dose-response relationships between insulin and intermediary metabolites were sought by analysis of variance applied to regression. For insulin (log) and glucose the slope of the relationship was significantly shallower in the oral contraceptive group. For insulin (log) and non-esterified fatty acids the slopes of the regression lines were not different between groups but lines were significantly displaced. For insulin (log) and total ketone bodies (log) slopes of the regression lines were not different but significant displacement was observed. At identical insulin concentrations women taking an oral contraceptive had higher non-esterified fatty acids (NEFA) (difference between groups +0.15 mmol/l, P less than 0.001) and total ketone bodies (log: -0.26 mmol/l, P less than 0.001). The potency of insulin action in oral contraceptive users versus the luteal group was 0.47 (P less than 0.01) for NEFA and 0.38 (P less than 0.001) for total ketone bodies. The results demonstrate, for the first time, in-vivo insulin resistance of NEFA and ketone bodies' metabolism induced by oral contraceptive use.
Adult↗
The metabolic effects of fatal cyanide poisoning.
Metabolic and toxicological data were obtained during the first 24 hours following severe and eventually fatal cyanide poisoning. Initial blood cyanide concentrations were 804 mumol/l but fell rapidly over 24 hours following cobalt edetate therapy to 15 mumol/l. However, plasma thiocyanate concentrations rose over 24 hours (147-267 mumol/l) suggesting continued tissue detoxification. The major metabolic abnormality was lactic acidosis (initial pH 7.21, blood lactate 17.5 mmol/l) which corrected over 12 hours. Despite high circulating insulin concentrations the responses of blood glucose, plasma non-esterified fatty acid, blood glycerol and 3-hydroxybutyrate suggested marked insulin resistance.
Acidosis, Lactic↗
The effects of verapamil, diltiazem, nifedipine and propranolol on metabolic control in hypertensives with non-insulin dependent diabetes mellitus.
The effects of one month's treatment with each of nifedipine, verapamil, diltiazem, propranolol and placebo, given in random order, on fasting plasma glucose, haemoglobin Alc, serum fructosamine, immunoreactive insulin, cholesterol, and triglyceride were studied in a group of 19 patients with hypertension and non-insulin dependent diabetes mellitus. The metabolic effects of the active drugs were generally small but fasting plasma glucose was increased by propranolol from 9.3 +/- 3.0 to 10.4 +/- 3.4 mmol/l (P less than 0.01) (mean +/- SD) and to 10.1 +/- 3.2 mmol/l (P less than 0.05) by nifedipine. Serum fructosamine was increased from 2.75 +/- 0.53 to 2.89 +/- 0.62 mmol/l (P less than 0.05) by diltiazem and to 2.91 +/- 0.65 (P less than 0.05) by propranolol. Verapamil increased fasting serum immunoreactive insulin: diltiazem and propranolol tended to reduce it. Propranolol but not the other drugs significantly increased serum triglyceride. Calcium antagonists may be preferable to beta adrenoceptor blockers for the treatment of hypertensive diabetics. Of the three calcium antagonists we studied, verapamil may have advantages over nifedipine and diltiazem.
Aged↗
Following weight loss in massively obese patients correction of the insulin resistance of fat metabolism is delayed relative to the improvement in carbohydrate metabolism.
Intermediary metabolite and serum insulin concentrations have been measured during incremental intravenous low-dose insulin infusion in massively obese patients before, and 3 months and 12 months after gastroplasty. Fasting blood glucose was similar on the three occasions, but fasting serum insulin was significantly higher preoperatively and showed a progressive fall with weight loss. Significant negative linear correlations were found between serum insulin and blood glucose, plasma nonesterified fatty acids, blood glycerol and blood total ketone bodies concentrations. The insulin-glucose dose-response curve showed a significant left shift at 3 months with a further significant improvement at 12 months. No significant change in the responses for nonesterified fatty acids, glycerol, and ketone bodies was observed at 3 months, but all three showed a significant left shift at 12 months. Massively obese patients are resistant to the action of insulin on carbohydrate and fat metabolism. Weight loss following gastroplasty results in an improvement in sensitivity to insulin, which is evident earlier in carbohydrate metabolism than in fat metabolism.
Adult↗