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Biomedical subjects

K G Alberti

Publications and source records attributed to K G Alberti.

At least 19 recordsLinked to original sources

Is diabetes mellitus related to undernutrition in rural Tanzania?

OBJECTIVE: To investigate the relation between undernutrition and diabetes. DESIGN: Survey of glucose tolerance in rural Tanzania. SETTING: Eight villages in three widely separated regions of Tanzania. SUBJECTS: 8581 people aged 15 and above: 3705 men and 4876 women. MAIN OUTCOME MEASURES: Oral glucose tolerance, body mass index, height, and low haemoglobin and cholesterol concentrations. RESULTS: In the eight villages 42.7-56.9% of all men and 30.0-45.2% of all women had a body mass index below 20 kg/m2; the lowest quintile was 18.2 kg/m2 in men and 18.6 kg/m2 in women. The prevalence of diabetes did not change significantly from the lowest to the highest fifths of body mass index in men (lowest 1.6% (95% confidence interval 0.8% to 2.9%) v highest 1.3% (0.7% to 2.5%)) or women (1.1% (0.6% to 2.1%) v 0.5% (0.2% to 1.2%)). In men and in women prevalence of impaired glucose tolerance was greater in the lowest fifths of height (8.2% (6.3% to 10.6%), and 11.1% (9.2% to 13.3%)) respectively and body mass index (9.6% (7.5% to 12.1%), and 8.4% (6.7% to 10.5%)) than in the highest fifths (impaired glucose tolerance 4.7% (3.4% to 6.5%); and 5.1% (3.9% to 6.7%); body mass index 5.1% (3.7% to 7.0%), and 7.7% (6.2% to 9.6%). CONCLUSION: Rates of diabetes were not significantly associated with low body mass index or height, but overall rates were much lower than those in well nourished Western populations. Increased impaired glucose tolerance in the most malnourished people may reflect the larger glucose load per kilogram weight. The role of undernutrition in the aetiology of diabetes must be questioned.

Adolescent

Serum triglyceride and insulin levels are associated with erythrocyte sodium-lithium counter-transport activity in normoglycaemic individuals.

The relationship between erythrocyte sodium-lithium counter-transport activity, serum insulin, lipids and demographic factors was examined in 93 normoglycaemic predominantly normotensive individuals with mild fasting hypercholesterolaemia (greater than 5.2 mmol/l). The major significant univariate correlates of sodium-lithium counter-transport activity were fasting serum triglycerides, HDL cholesterol, the ratio of fasting glucose: insulin, apo A1, alcohol consumption and apo B. Stepwise multiple regression analysis revealed 24% of the variability in sodium-lithium counter-transport activity could be accounted for by independent contributions of fasting serum triglycerides, alcohol consumption, the fasting glucose/insulin ratio and apo A1 and ANOVA confirmed a significant relationship with fasting insulin measures that was independent of serum triglycerides (P less than 0.05). The relationship between erythrocyte sodium-lithium counter-transport activity and concentrations of serum triglycerides, HDL components, insulin and additionally alcohol consumption, could reflect the influence of those variables on erythrocyte structure and function.

Alcohol Drinking

Electrocardiographic abnormalities and associated factors in Chinese living in Beijing and in Mauritius. The Mauritius Non-Communicable Disease Study Group.

OBJECTIVE: To compare the prevalence of electrocardiographic abnormalities and to evaluate the association between these abnormalities and the levels of coronary heart disease among Chinese living in different environments. DESIGN: Cross sectional surveys. SETTING: Beijing, China, and the island of Mauritius. SUBJECTS: Random samples of people aged 35-64 years in Beijing (621 men, 642 women) in 1984 and in Mauritius among Chinese (137 men, 130 women) and non-Chinese (1265 men, 1432 women) in 1987. MAIN OUTCOME MEASURES: Prevalence of electrocardiographic abnormalities suggesting coronary heart disease and of associated risk factors. RESULTS: Prevalence of electrocardiographic abnormalities suggesting coronary heart disease was significantly lower in Beijing (4.0%) than in Mauritian Chinese (24.3%) and Mauritian non-Chinese (24.5%). Mean serum concentrations of total and non-high density lipoprotein cholesterol were lower in Beijing Chinese than in Mauritian Chinese, but smoking and hypertension were slightly more prevalent. Overall, men with electrocardiographic abnormalities had higher risk factor levels than those with a normal electrocardiogram regardless of ethnic origin. CONCLUSIONS: The prevalence of coronary heart disease and associated risk factors was different among Chinese living in two different environments: in Beijing in the People's Republic of China and in Mauritius. Chinese, who traditionally have a very low frequency of coronary heart disease, are by no means protected against coronary heart disease and other non-communicable diseases. Therefore, primary prevention of coronary heart disease is a major challenge for preventive medicine in China, as well as in many other developing countries.

Adult

A simple, sensitive technique for classification of apolipoprotein(a) isoforms by sodium dodecyl sulphate-polyacrylamide gel electrophoresis.

Lipoprotein(a) (Lp(a)) is a lipoprotein containing a unique glycoprotein, apolipoprotein(a) (apo(a)), which shows considerable heterogeneity of apparent molecular mass on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). A unifying classification of isoform has been lacking. A simple sensitive procedure for classifying apo(a) isoforms was developed in which the relative mobility of apo(a) on SDS-PAGE was related to that of apolipoprotein (apo) B-100 (Rf vs B). After Western blotting apo(a) bands were visualised by a sensitive double antibody technique employing commercial polyclonal antibodies (sheep antihuman Lp(a) antibody, alkaline phosphatase-linked donkey antisheep antibody). The technique was sensitive (lower limit of detection 0.02 micrograms apo(a)) and had good reproducibility (coefficient of variation 0.9-6.4%). Ten isoform mobilities are described (less than 0.35, 0.40, 0.50, 0.60, 0.70, 0.80, 1.0, 1.10, greater than 1.15). Individuals may have single or double band phenotypes. This classification is compatible with those previously described and the method is suitable for many laboratories, as it employs standard equipment and commercially available materials.

Apolipoproteins A

Microalbuminuria and associated cardiovascular risk factors in the community.

The prevalence of microalbuminuria and relationship to cardiovascular risk factors was examined in a cross-sectional community survey of cardiovascular risk factors. Microalbuminuria (when classified as albumin concentration greater than 20 micrograms/ml) was present in 6.3% of subjects but in conjunction with an albumin/creatinine ratio greater than 3.5 in only 2.2%. Diastolic blood pressure, prevalence of abnormal electrocardiographs, and to a lesser extent systolic blood pressure and fibrinogen concentration, were greater in those with albuminuria concentrations greater than 20 micrograms/ml. The strongest positive univariate correlates of albumin/creatinine ratios in those with detectable albuminuria were age, fibrinogen, blood pressure, total- and low density lipoprotein-(LDL) cholesterol, apo B and alcohol intake, whereas fasting insulin and insulin resistance were inversely correlated. Multiple regression analysis revealed that age, gender, systolic blood pressure and insulin resistance independently accounted for 37% of the variability in albumin/creatinine ratios. When those 10 subjects with microalbuminuria and albumin/creatinine ratios greater than 3.5 were matched with 20 with normoalbuminuria for age, gender and body mass index, the microalbuminuric subjects had significantly lower LDL cholesterol/apo B ratios and a tendency to lower high density lipoprotein (HDL) cholesterol and HDL cholesterol/apo A1 ratios. Microalbuminuria is uncommon in the general population, and is related to ageing, blood pressure and other vascular risk factors. It may reflect the presence of established cardiovascular disease.

Adult

Gliclazide: metabolic and vascular effects--a perspective.

Gliclazide is a second-generation sulfonylurea that is widely used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It has been recommended for use on the basis of both its metabolic and nonmetabolic effects. It has a clear beneficial effect on metabolic control in NIDDM. Blood glucose and lipid levels are lowered. The glucose-lowering effects are secondary to both enhanced insulin secretion and a decrease in insulin resistance. The former is due to closure of a K+ adenosine triphosphate (ATP) channel in the beta cell. The mechanism whereby insulin action on the liver and muscle are potentiated remains unknown. It does not appear to involve the insulin receptor, and although glycogen synthase activation is enhanced, this is probably not specific. It has proven difficult to separate the metabolic effects of gliclazide from the effects of improved control. The metabolic actions are probably also shared with other sulfonylureas. Gliclazide also has beneficial effects on platelet behavior and function and on the endothelium, in addition to improving free radical status. These effects should be beneficial for the prevention of diabetic microangiopathy and macroangiopathy. Some evidence has appeared for the prevention of deterioration of diabetic retinopathy, but results are variable and more convincing studies are required. Many of the nonmetabolic effects of gliclazide appear to be unique to this agent. Gliclazide thus appears to be a reasonable choice in the treatment of NIDDM with diet failure, both from the metabolic and nonmetabolic standpoint.

Cardiovascular Diseases

Effect of acute inhibition of lipolysis on operation of the glucose-fatty acid cycle in hepatic cirrhosis.

Hepatic cirrhosis is frequently associated with glucose intolerance and insulin resistance, but the mechanisms underlying the insulin insensitivity are unknown. Plasma concentrations of nonesterified fatty acids (NEFA) are typically elevated in cirrhosis, and the glucose-fatty acid cycle provides a mechanism by which fatty acids may play a role in regulating glucose metabolism. We have therefore investigated the effect of acute inhibition of lipolysis, using the nicotinic acid analogue, acipimox, in 10 male patients with cirrhosis. All subjects were studied in the postabsorptive state after a 10- to 12-hour fast and were given either acipimox 250 mg or a placebo orally 2 hours before a 75-g oral glucose tolerance test (OGTT) and an infusion of insulin (50 mU/kg/h) and glucose (6 mg/kg/min) (insulin sensitivity tests [IST]). The drug was taken in a double-blind crossover design for each test. During the 2 hours following acipimox, there were rapid decreases in plasma NEFA, glycerol, and 3-hydroxybutyrate, confirming inhibition of lipolysis, while there were significant decreases in glucose, insulin, and C-peptide (P less than .001) compared with patients receiving the placebo. Acipimox blunted the increase in glucose after oral glucose loading and decreased incremental glucose concentration (from 579 +/- 76 to 445 +/- 65 mmol/min/L, P less than .02) and incremental insulin concentration (from 13.4 +/- 2.5 to 9.0 +/- 1.4 U/min/L, P = .056) in the OGTT. Improvements in classification of glucose tolerance were seen in five subjects. During the IST, significant reductions occurred in steady-state blood glucose (to 8.8 +/- 1 mmol/L, P less than .02) and C-peptide (to 3.0 +/- 0.5 nmol/L, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid

Is diabetes always diabetes?

Diabetes is always taken to be a life-long diagnosis. In order to re-examine this question, 75 g glucose tolerance tests (OGTT) were performed twice on 37 previously confirmed diabetic patients (mean duration of diabetes of 4.6 years; range 1-15 years) with normal glycosylated haemoglobin levels on regular review. Weight loss since institution of a healthy diet was 7.6 +/- 4.8 kg (+/- SE). Normal glucose tolerance was found in 27% of patients and impaired glucose tolerance in 21% with no significant change on rechallenge. HbA1 was 6.3 +/- 1.5% (+/- SD) (normal < 7.5%) in patients with normal glucose tolerance compared to 7.0 +/- 0.9% (+/- SD) in those with impaired glucose tolerance, P < 0.05. The response of the OGTT in these patients varied with dietary intake and weight. Such individuals could be regarded as having perfectly controlled diabetes or alternatively to have been cured. The definition of diabetes should be reviewed to allow people to escape the diagnosis where permanent change in dietary habits is established.

Blood Glucose

The ketosis-resistance in fibro-calculous-pancreatic-diabetes. 1. Clinical observations and endocrine-metabolic measurements during oral glucose tolerance test.

We measured circulating levels of C-peptide, pancreatic glucagon, cortisol, growth hormone and metabolites (glucose, non-esterified fatty acids, glycerol and 3-hydroxybutyrate) in fibro-calculous-pancreatic diabetic (FCPD, n = 28), insulin-dependent diabetic (IDDM, n = 28) and non-diabetic control (n = 27) subjects during an oral glucose tolerance test. There was no difference in the two diabetic groups in age (FCPD 24 +/- 2, IDDM 21 +/- 2 years, mean +/- SEM), BMI (FCPD 16.0 +/- 0.6, IDDM 15.7 +/- 0.4 kg/m2), triceps skinfold thickness (FCPD 8 +/- 1, IDDM 7 +/- 1 mm), glycaemic status (fasting plasma glucose, FCPD 12.5 +/- 1.5, IDDM 14.5 +/- 1.2 mmol/l), fasting plasma C-peptide (FCPD 0.13 +/- 0.03, IDDM 0.08 +/- 0.01 nmol/l), peak plasma C-peptide during OGTT (FCPD 0.36 +/- 0.10, IDDM 0.08 +/- 0.03 nmol/l) and fasting plasma glucagon (FCPD 35 +/- 4, IDDM 37 +/- 4 ng/l). FCPD patients, however, showed lower circulating concentrations of non-esterified fatty acids (0.73 +/- 0.11 mmol/l), glycerol (0.11 +/- 0.02 mmol/l) and 3-hydroxybutyrate (0.15 +/- 0.03 mmol/l) compared to IDDM patients (1.13 +/- 0.14, 0.25 +/- 0.05 and 0.29 +/- 0.08 mmol/l, respectively). This could be due to enhanced sensitivity of adipose tissue lipolysis to the suppressive action of circulating insulin and possibly also to insensitivity of hepatic ketogenesis to glucagon. Our results also demonstrate preservation of alpha-cell function in FCPD patients when beta-cell function is severely diminished, suggesting a more selective beta-cell dysfunction or destruction than hitherto believed.

3-Hydroxybutyric Acid

The effect of intraperitoneal insulin delivery on carbohydrate metabolism in type 1 (insulin-dependent) diabetic patients.

Patients with type 1 diabetes are usually given insulin subcutaneously, but this does not mimic the physiological route of pancreatic insulin release, which may be better achieved with intraperitoneal insulin. Five C-peptide negative type 1 diabetic patients were studied on two occasions, once with intravenous (IV) and once with intraperitoneal (IP) insulin. Normoglycaemia was maintained from 1700 h with variable insulin infusion, and glucose turnover and recycling assessed from 0600 to 0800 h. A 4-h hyperinsulinaemic (25 mU kg-1 h-1) euglycaemic clamp was then performed, with IP or IV insulin delivery. During the night similar insulin infusion rates were needed to achieve equal blood glucose concentrations. Glucose turnover was identical (IV: 2.4 +/- 0.2 vs IP: 2.3 +/- 0.1 mg kg-1 min-1) (+/- SE) with glucose/carbon recycling 8.8 +/- 4.7 and 12.8 +/- 2.9% (NS). Blood lactate, pyruvate and alanine concentrations were significantly higher with IP than IV insulin (P less than 0.05). During the clamp, insulin concentration was 28 +/- 3 mU/l with IV insulin and 15 +/- 1 mU/l with IP insulin (P less than 0.05) and glucose requirement 2.0 +/- 0.5 and 0.8 +/- 0.3 mg kg-1 min-1, respectively (P less than 0.05). Glucose carbon recycling was higher with IP insulin (P less than 0.05). We conclude that: (1) in type 1 (insulin-dependent) diabetic patients hepatic glucose production could be normalized with both routes of insulin administration, and (2) at the same insulin infusion rate, the relative peripheral hypoinsulinaemia with IP route is sufficient to increase the rate of release of gluconeogenic precursors, or decrease their hepatic uptake.

Adult

Acute metabolic and hormonal responses to the inhibition of lipolysis in non-obese patients with non-insulin-dependent (type 2) diabetes mellitus: effects of acipimox.

1. Increased rates of fatty acid oxidation are frequently observed in patients with non-insulin-dependent diabetes mellitus and may contribute to hyperglycaemia by both decreasing peripheral glucose disposal and, more importantly, by increasing the rate of gluconeogenesis and therefore hepatic glucose output. Despite this relationship between lipid and carbohydrate metabolism, fasting glucose concentrations do not fall acutely in patients with non-insulin-dependent diabetes mellitus when plasma non-esterified fatty acid concentrations and lipid oxidation rates are decreased, questioning the importance of this interaction to glycaemic control. We have therefore measured the acute changes that occur 120-150 min after administration of 500 mg of the antilipolytic agent acipimox in eight non-obese male patients with non-insulin-dependent diabetes mellitus. 2. After administration of acipimox, lipolysis was inhibited as reflected by lower plasma non-esterified fatty acid (0.05 +/- 0.02 versus 0.55 +/- 0.05 mmol/l, P less than 0.001) and blood glycerol (8 +/- 1 versus 56 +/- 8 mumol/l, P less than 0.001) concentrations. The lipid oxidation rate was decreased (0.63 +/- 0.05 versus 1.02 +/- 0.08 mg min-1 kg-1, P less than 0.001), whereas there was a significant increase in the carbohydrate oxidation rate (1.93 +/- 0.17 versus 1.22 +/- 0.18 mg min-1 kg-1, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid

A double blind study of the effect of acipimox on serum lipids, blood glucose control and insulin action in non-obese patients with type 2 diabetes mellitus.

Hyperlipidaemia, in particular raised concentrations of serum triglycerides, together with raised plasma non-esterified fatty acid concentrations, is common in patients with Type 2 (non-insulin-dependent) diabetes mellitus and may be associated with insulin insensitivity. Thirty non-obese Type 2 diabetic patients (15 controlled with diet alone and 15 with diet plus oral sulphonylurea therapy) were therefore recruited to take part in a double-blind, randomized, crossover comparison of acipimox (250 mg three times daily for 3 months) and placebo. Serum lipids, blood glucose control, insulin sensitivity, and glucose tolerance were measured before and after each treatment period. There was a significant decrease in serum triglycerides (2.05 +/- 1.08 vs 2.91 +/- 1.75: p < 0.005), cholesterol (5.66 +/- 1.02 vs 6.26 +/- 1.17: p = 0.0005), and apoprotein B (1.32 +/- 0.23 vs 1.44 +/- 0.25: p < 0.05) while HDL cholesterol and apoprotein A-1 concentrations were unchanged. There was no change in blood glucose control measured by fasting glucose, insulin, and HBA, concentrations, but there was a significant improvement in insulin action assessed by glucose-insulin infusion. Although plasma non-esterified fatty acid concentrations were lower during the oral glucose tolerance test after acipimox, there was no difference in either the peak or 2-h plasma glucose concentrations and the total area under the glucose curve did not change. Acipimox was well tolerated and no patients withdrew from the study for drug-related symptoms. Thus, acipimox effectively lowers serum cholesterol and triglycerides in patients with Type 2 diabetes without adversely altering blood glucose control, and appears to improve insulin sensitivity.

Analysis of Variance

A survey of lower limb amputation in diabetic patients.

A retrospective survey of non-traumatic and non-neoplastic lower limb amputations in Newcastle upon Tyne during 1989-91 was performed. Hospital data were cross-checked with the local limb fitting centre to ensure 100% ascertainment. The diabetic patients were found to be 39% of amputees and 42% of operations (all levels). Incidence of diabetes amputation was 5.7 per 100,000 population per year. Fifteen percent of the diabetic patients had diabetes first diagnosed when they were admitted for amputation. For the known diabetes patients, 46% were under diabetes care by general practitioners only. Forty-seven percent of the patients who were under the care of a hospital service for diabetes had incomplete foot examination and assessment. Mortality rate within 30 days after diabetic amputation was 10% and median life expectancy following amputation was 22 months. It seems likely that assessment and management of the diabetic foot remains suboptimal in Newcastle, and that protocols and audit of care could lead to improvements without additional resources.

Aged

The short insulin tolerance test for determination of insulin sensitivity: a comparison with the euglycaemic clamp.

The glucose clamp technique is currently regarded as the standard test for measuring insulin sensitivity against which other methods are compared but is unsuitable for routine screening of patients outside a hospital base. There is thus a need for a simpler test to measure insulin sensitivity. We have therefore compared the glucose disappearance rate KITT in the first 15 min of the insulin tolerance test (ITT) with the M and M/I values derived from the standard euglycaemic clamp in nine normal subjects and eight subjects with Type 2 (non-insulin dependent) diabetes mellitus and coexisting obesity. All subjects underwent the ITT and euglycaemic clamp in random order. Nine subjects later had a repeat ITT to determine the reproducibility of the test. In the ITT, 0.1 U kg-1 body weight, human Actrapid insulin was given as an IV bolus and simultaneous arterialized and venous blood samples were obtained every minute for 15 min. The first order rate constant for the disappearance of glucose KITT over the period 3-15 min was taken as a measure of insulin sensitivity. The euglycaemic clamp was performed with an insulin infusion of 50 mU kg-1 h-1 for 120 min and a variable rate glucose infusion to maintain blood glucose concentration at 0.5 mmol l-1 below fasting level to minimize the effect of endogenous insulin secretion. The ratio of the mean rate of glucose infused (M, mumol kg-1 min-1) to the plasma insulin over the last 30 min of the clamp was taken as a measure of tissue sensitivity to insulin (M/I) assuming endogenous glucose output was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Lipid and lipoprotein metabolism in familial combined hyperlipidaemia during treatment of sporadic phaeochromocytoma: a case study.

Lipid metabolism was evaluated during management of phaeochromocytoma in a 41 year old non-obese post-menopausal women with familial combined hyperlipidaemia. The main effect of the excess catecholamine secretion on lipid metabolism was increased lipolytic activity, lower serum triglyceride and increased HDL cholesterol concentrations, compared with findings following removal of the tumour. Before removal of the tumour, the use of beta blockers alone led to marked deterioration of the hyperlipidaemic state, and combined alpha and beta blockade additionally led to a marked reduction in fat oxidation and lipoprotein lipase activity. Overactivity of the adrenergic system leads to changes in lipid metabolism in phaeochromocytoma. Treatment of the phaeochromocytoma may lead to worsening of hyperlipidaemia pre-existing in such individuals.

Adrenal Gland Neoplasms

Dose-response characteristics of human proinsulin and insulin in non-insulin-dependent diabetic humans.

We compared the actions of human proinsulin and insulin on glucose turnover and on intermediary carbohydrate and lipid metabolism in non-insulin-dependent diabetes mellitus (NIDDM). Six diet-controlled weight-matched (25.4 +/- 1.0 kg/m2) NIDDM subjects underwent six separate isoglycemic clamps. Glucose turnover was measured using a primed continuous infusion of [6',6'-2H2]glucose. Each subject received three low-dose intravenous infusions of both insulin and proinsulin. Blood glucose was maintained at 6.7 +/- 0.3 mM during proinsulin and insulin infusion. Insulin (I) infusions gave steady-state levels of 0.12 +/- 0.001 (I1), 0.18 +/- 0.01 (I2), and 0.33 +/- 0.01 nM (I3). Steady-state proinsulin (P) levels were 2.5 +/- 0.1 (P1), 4.3 +/- 0.2 (P2), and 8.8 +/- 0.9 nM (P3). Hepatic glucose production was suppressed equally by proinsulin and insulin at all doses. The metabolic clearance rate of glucose was significantly increased during the insulin infusion compared with proinsulin. The use of [6',6'-2H2]glucose resulted in a mean underestimation of the glucose infusion rate of 10.0 +/- 4.0 and 6.0 +/- 2.5% during the two highest insulin and proinsulin doses, respectively. Proinsulin had a significantly weaker effect than insulin, at the lowest infusion dose, in percent suppression of plasma nonesterified fatty acids, blood glycerol, and beta-hydroxybutyrate levels (all P less than 0.05). Blood lactate levels were lower during the P1 (628 +/- 43 microM) and P2 (657 +/- 93 microM) infusions compared with I1 (776 +/- 60 microM) and I2 (878 +/- 44 microM; P less than 0.05, P less than 0.02), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2