Circulating lipids and cardiovascular risk in newly diagnosed non-insulin-dependent diabetic subjects in India.

Circulating concentrations of total cholesterol, triglycerides, non-esterified fatty acids (NEFA), glycerol, and 3-hydroxybutyrate (3-HB) were measured in 133 subjects with normal glucose tolerance (NGT), 78 with impaired-glucose-tolerance (IGT) and 189 non-insulin dependent (Type 2) diabetic (NIDDM) patients. Plasma cholesterol concentration was similar in the three groups; NGT (4.2 (2.3-7.5) mmol l-1, median (range)), IGT (4.7 (2.7-6.3)) and NIDDM (4.3 (2.3-6.9)). Plasma triglycerides (NGT 0.88 (0.37-2.80), IGT 1.26 (0.43-3.82) and NIDDM 1.38 (0.62-3.91) mmol l-1) and NEFA (NGT 0.81 (0.29-1.58), IGT 1.02 (0.33-1.87) and NIDDM 1.02 (0.48-2.77) mmol l-1) were higher in the two hyperglycaemic groups, but blood 3-HB concentration was similar in the three groups. Plasma cholesterol concentration in these subjects is lower than that reported in white Caucasians in the UK and USA and migrant Indian NIDDM patients in the UK. In NIDDM patients plasma cholesterol concentration was related to age, body mass index (BMI), and plasma glucose concentration while plasma triglyceride concentration was related to plasma NEFA and insulin (IRI) concentration. Evidence of ischaemia on electrocardiography in patients with diabetes was associated with higher age, blood pressure, plasma triglyceride, glucose, and IRI concentrations.

Ketosis resistance in fibrocalculous pancreatic diabetes: II. Hepatic ketogenesis after oral medium-chain triglycerides.

A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not become ketotic even in adverse conditions. It is not clear whether this ketosis resistance is due to reduced fatty acid release from adipose tissue or to impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and compared it with that in matched insulin-dependent diabetes mellitus (IDDM) patients and healthy controls. After oral MCTs, FCPD patients showed only a mild increase in blood 3-hydroxybutyrate (3-HB) concentrations (median: fasting, 0.13 mmol/L; peak, 0.52) compared with IDDM patients (fasting, 0.44; peak, 3.39) and controls (fasting, 0.04; peak, 0.75). Plasma nonesterified fatty acid (NEFA) concentrations were comparable in the two diabetic groups (FCPD: fasting, 0.50 mmol/L; peak, 0.79; IDDM: fasting, 0.91; peak, 1.04). Plasma C-peptide concentrations were low and comparable in the two diabetic groups. Plasma glucagon concentrations were higher in IDDM patients in the fasting state, but declined to levels comparable to those in FCPD patients after oral MCTs. Plasma carnitine concentrations were comparable in the two groups of patients. It is concluded that the failure to stimulate ketogenesis under these conditions could be partly due to inhibition of a step beyond fatty acid entry into the mitochondria.

Fibrocalculous pancreatic diabetes in Pune, India. Clinical features and follow-up for 7 yr.

OBJECTIVE: To study clinical features of fibrocalculous pancreatic diabetes from this clinic, to compare these with the published criteria of malnutrition-related diabetes mellitus, and to conduct serial follow-up of these patients to study difficulties in their treatment. RESEARCH DESIGN AND METHODS: Details of presenting symptoms, anthropometry, diabetic tissue damage, treatment, and follow-up of 55 patients with fibrocalculous pancreatic diabetes (pancreatic calculi demonstrated on X-ray and sonography) treated during the last 7 yr were studied. RESULTS: Many patients did not fit the accepted criteria of malnutrition-related diabetes. Thus, 17 (31%) were diagnosed after 30 yr of age and 23 (42%) had a body mass index > 18 kg/m2, and the daily dose of insulin in these patients (mean 0.8 U/kg) was similar to that in the IDDM patients (mean 1.0 U/kg). The two pathognomonic complaints (pancreatic pain and steatorrhea) were not always present. Many patients took very irregular treatment, but none suffered diabetic ketoacidosis despite stopping insulin for long periods of time; 33% of patients had some diabetic tissue damage when first seen. Fourteen patients were lost to follow-up, and 11 died during the follow-up. CONCLUSIONS: Clinical features of these fibrocalculous pancreatic diabetes patients were somewhat different than the classic descriptions. A need exists to reconsider classification of FCPD under malnutrition-related diabetes mellitus. Many patients receive irregular treatment, and a substantial proportion die within a few years of diagnosis, many as a result of preventable causes.

The relationship between obesity, plasma immunoreactive insulin concentration and blood pressure in newly diagnosed Indian type 2 diabetic patients.

The association of blood pressure with clinical and biochemical measures was studied in 185 newly diagnosed Type 2 diabetic patients, 74 impaired-glucose-tolerant (IGT) and 128 non-diabetic control subjects. Hyperglycaemic subjects were older than control subjects (controls 40 (24-59) years, IGT 48 (29-64) years, diabetic 43 (29-60) years, median (5th-95th centile) both p < 0.05). They were also more obese (body mass index (BMI) controls 23.5 kg m-2 (17.2-29.9), IGT 26.0 kg m-2 (19.8-33.9), diabetic 24.2 kg m-2 (19.3-32.2)) and with a greater waist-hip ratio (controls 0.83 (0.70-0.98), IGT 0.88 (0.75-0.98), diabetic 0.89 (0.75-1.00)). Blood pressure was significantly higher in both IGT (systolic 127 mmHg (108-162), diastolic 84 mmHg (66-99)) and diabetic patients (systolic 130 mmHg (104-160), diastolic 84 mmHg (66-102)) compared to non-diabetic controls (systolic 120 mmHg (100-151), diastolic 80 mmHg (60-94)). Univariate analysis showed that in diabetic patients systolic blood pressure was related to age (r = 0.17, p < 0.05), BMI (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting and post glucose, r = approximately 0.25, p < 0.01) but not to C-peptide concentrations; diastolic blood pressure to BMI (r = 0.35, p < 0.001), waist-hip ratio (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting r = 0.30, p < 0.001, post glucose r = approximately 0.20, p < 0.05) but not to C-peptide concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary albumin excretion rate (AER) in newly-diagnosed type 2 Indian diabetic patients is associated with central obesity and hyperglycaemia.

Urinary albumin excretion rate (AER) was measured in non-diabetic controls (n = 143) and newly diagnosed impaired glucose tolerant (IGT, n = 64) and non-insulin-dependent (type 2) diabetic patients (n = 146). AER progressively increased from non-diabetic [3.7 (1.1-51.3) micrograms/min, median (5-95th centile)] to IGT [4.8 (1.3-53.7)] and diabetic [7.3 (1.4-91.6)] groups. Eight percent of non-diabetic, 19% of IGT and 23% of type 2 diabetic patients showed 'microalbuminuria' (AER, 20-200 micrograms/min) (non-diabetic vs diabetic P less than 0.01, non-diabetic vs IGT NS, IGT vs diabetic NS). AER was directly related to waist-hip ratio (P less than 0.001) and HbA1 (P less than 0.01) in diabetic patients; 80% of diabetic patients with microalbuminuria were men (P less than 0.06 compared to 'normoalbuminuric' diabetic patients). Association of AER with waist-hip ratio was present in men as well as women. Thus, in the newly diagnosed type 2 Indian diabetic patients AER is associated with central obesity in addition to its well known association with hyperglycaemia. Our findings offer a possible explanation for the increased risk of proteinuria in diabetic men than in women because men are centrally more obese. It could also explain previous reports of higher AER in migrant Asian diabetic patients in the U.K. compared to native white Caucasian diabetic patients because Asians are known to be more centrally obese.

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.

Central rather than generalized obesity is related to hyperglycaemia in Asian Indian subjects.

The relationship of body mass index and waist-hip ratio with plasma glucose concentrations during an oral glucose tolerance test (OGTT) was studied in native Indian (Asian) subjects. A total of 389 subjects (131 non-diabetic, 74 impaired glucose tolerant (IGT) and 184 Type 2 diabetic (newly diagnosed and untreated] were studied. Prevalence of obesity (BMI greater than or equal to 27.0 kg m-2 in men and greater than or equal to 25.0 kg m-2 in women, 21% and 47%, respectively) was lower in people with Type 2 diabetes than that reported in white Caucasian and migrant Asian populations. Body mass index was highest in IGT subjects (26.1 (19.7-34.3) kg m-2, median (5-95th centile] and was higher in diabetic subjects (24.2 (19.3-32.2) kg m-2) than in non-diabetic control subjects (23.5 (17.1-30.0) kg m-2). However, waist-hip ratio was higher in both IGT (0.88 (0.75-0.98)) and diabetic subjects (0.88 (0.75-1.00)) than in non-diabetic control subjects (0.83 (0.70-0.97)), with no difference between the hyperglycaemic groups. On multivariate analysis, fasting as well as 2-h plasma glucose concentrations during OGTT were found to be related to waist-hip ratio (p less than 0.01) and subscapular fat thickness (p less than 0.01) but not to body mass index (or triceps fat thickness). Thus, in native Indians central obesity seems to be a more important association of hyperglycaemia than generalized obesity.

Exocrine pancreatic function (serum immunoreactive trypsin, fecal chymotrypsin, and pancreatic isoamylase) in Indian diabetics.

Forty-nine patients with tropical calcific pancreatitis (TCP), 51 insulin-dependent diabetics (IDDMs), 87 non-insulin-dependent diabetics (NID-DMs), and 66 nondiabetic controls were studied to evaluate their exocrine pancreatic function by measurement of serum immunoreactive trypsin (IRT, normal for white caucasians from the U.K. of 140-414 micrograms/L), pancreatic isoamylase (PIA, normal of 35-125 U/L), and fecal chymotrypsin (FCT, normal of greater than 6.6 u/g). The majority of patients were studied within 1 year of diagnosis. TCP subjects included 7 nondiabetics, 6 with impaired glucose tolerance (IGT-TCP), and 36 diabetics [fibrocalculous pancreatic diabetes (FCPD)]. There was evidence of active pancreatitis (IRT greater than 800 micrograms/L) and partial preservation of function in nondiabetic TCP subjects [median IRT of 220 micrograms/L (range of 102-1,360 micrograms/L), FCT of 2.2 u/g (range 0.7-12.8 u/g)] and also in IGT-TCP subjects [IRT of 370 micrograms/L (range of 30-1,360 micrograms/L), FCT of 4.2 u/g (range of 1-38 u/g)]. FCPDs showed severely diminished exocrine function [IRT of 50 micrograms/L (range of 0-184 micrograms/L), FCT of 0.23 u/g (range of 0-10.4 u/g)]; none showed IRT greater than 800 micrograms/L. IDDMs and NIDDMs also showed diminished exocrine pancreatic function in approximately 30 and approximately 10%, respectively. Controls showed a wide range of IRT and FCT concentrations; IRT concentrations tended to be higher than those reported in white Caucasians from the U.K. Three controls, one IDDM, and two NIDDMs showed "pancreatic" IRT concentrations in the absence of symptoms. PIA concentrations were diminished in FCPD but were similar in IDDM and NIDDM subjects compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The spectrum of pancreatic exocrine and endocrine (beta-cell) function in tropical calcific pancreatitis.

Exocrine pancreatic marker (immunoreactive-trypsin) and endocrine Beta-cell function (plasma insulin and C-peptide during an oral glucose tolerance test) were studied in 40 subjects with tropical-calcific-pancreatitis [seven non-diabetic, seven with impaired-glucose-tolerance and 26 diabetic (fibro-calculous-pancreatic-diabetes)]. In non-diabetic and impaired-glucose-tolerance subjects there was evidence of active pancreatitis in some and exocrine function was partially preserved. Fibro-calculous-pancreatic-diabetic subjects showed severely diminished exocrine pancreatic function; none showed 'pancreatitic' elevation of immunoreactive-trypsin. Beta-cell function was preserved in non-diabetic and impaired-glucose-tolerance subjects; diabetic subjects showed variable Beta-cell function but it was severely diminished in more than 75%. Immunoreactive-trypsin and C-peptide were directly correlated (rs = 0.55, p less than 0.01). This cross sectional study demonstrates, for the first time, that the Beta-cell loss in tropical-calcific-pancreatitis is related to the exocrine loss. It suggests that diabetes in tropical-calcific-pancreatitis is either secondary to pancreatitis or that a common factor(s) acts simultaneously on both components.

Pancreatic C-peptide response to oral glucose in fibrocalculous pancreatic diabetes. Improvement after treatment.

beta-Cell function (plasma C-peptide) in 17 fibrocalculous pancreatic diabetic (FCPD) subjects (14 newly diagnosed) was not different at presentation from that in 14 matched insulin-dependent diabetic subjects. After insulin treatment and improvement in the patients' nutritional and metabolic status, fasting and postglucose plasma C-peptide concentrations showed a significant increase (fasting 0.06 +/- 0.01 to 0.17 +/- 0.03 nM, peak 0.11 +/- 0.02 to 0.29 +/- 0.06 nM, mean +/- SE; P less than 0.01 for both). Thus, severely diminished beta-cell function in FCPD is partially reversible after treatment. This could contribute to the clinical metabolic peculiarities of this group of patients.