Long-term effects of linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion

Summary We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200 g/min). Thirty-eight patients were randomly assigned to increase dietary polyunsaturated: saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products (n=18, two dropouts, analysis was performed in n=16) or to continue their usual diet (n=20). The total fat and protein content of the diet was unaltered. Clinical characteristics, albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7±4 to 11±2 energy % and polyunsaturated: saturated fatty acids ratio rose from 0.60±0.28 to 0.96±0.16 (p<0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p<0.02) and 55% (95% confidence interval, 11 to 127) (p<0.01) during the second year. Glomerular filtration rate remained unaltered and filtration fraction tended to rise (p<0.05 compared to usual diet group). In the usual diet group, albuminuria did not significantly increase by 16% (95% confidence interval, -17 to 38) and glomerular filtration rate declined during the second year. Blood pressure tended to rise similarly in both groups. Multiple regression analysis showed an independent effect of the high linoleic acid diet on the progression of albuminuria as well as the lack of decrease in glomerular filtration rate. Low density lipoprotein cholesterol and apolipoprotein B levels decreased in the high linoleic acid diet group (p<0.05). High density lipoprotein cholesterol declined in both groups (p<0.05). It is concluded that a linoleic-acid-enriched diet reduces atherogenic lipoproteins but does not have a beneficial effect on and might even promote renal functional abnormalities in Type 1 diabetic patients with elevated urinary albumin excretion.     

Urinary excretion of glycated albumin in insulin-dependent diabetic patients with normal urinary albumin excretion

Summary Glycation involves both circulating proteins, such as albumin, and structural proteins, such as the components of the glomerular basement membrane. A preferential excretion of glycated albumin (more anionic at physiological pH compared with unmodified plasma albumin) has been reported by some authors, but not by others. We therefore investigated the selectivity index (renal clearance of non-glycated albumin/clearance of glycated albumin) in 25 insulin-dependent diabetic patients with normal urinary albumin excretion and in 19 well-matched control subjects. The selectivity index was significantly higher in diabetic patients than in control subjects: 1.38±0.05 SEMvs 0.98±0.02, p<0.0001. This result is not consistent with a preferential urinary excretion of glycated albumin, at least in normoalbuminuric uncomplicated insulin-dependent diabetic patients.     

Apolipoprotein E genotype affects the response to lipid-lowering therapy in Chinese patients with type 2 diabetes mellitus

OBJECTIVE: To evaluate the effect of apolipoprotein E (apoE) genotype on baseline lipid levels and the response to hydroxy-methyl glutaryl coenzyme A reductase inhibitors (statins) therapy in Chinese patients with type 2 diabetes mellitus (DM). RESEARCH DESIGN AND METHODS: We consecutively recruited Chinese patients with type 2 DM requiring lipid-lowering therapy according to current guidelines. Patients were started on either simvastatin 10 mg daily or given an equivalent dose of lovastatin 20 mg. After 12 weeks of statin therapy, patients had fasting lipid profiles repeated. ApoE genotyping was performed by restriction fragment length polymorphism (RFLP). RESULTS: Ninety-six patients were studied. The epsilon3/epsilon3 genotype was in 62.5%, epsilon2/epsilon3 and epsilon3/epsilon4, 16.7 and 20.8%, respectively. After adjusting for confounding variables, baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in those with epsilon3/epsilon4 compared with epsilon2/epsilon3 genotype (6.7 vs. 5.5 mm for TC, 4.5 vs. 3.6 mm for LDL-C; p = 0.015 and p = 0.025, respectively). With statin therapy, epsilon3/epsilon4 patients had significantly greater LDL-C lowering compared with epsilon2/epsilon3 patients (48 vs. 27.7%; p = 0.04). There was no gender difference in baseline lipid parameters or response to statin therapy. CONCLUSIONS: ApoE genotype accounts for interindividual variability of baseline cholesterol levels, and response to statin therapy in Chinese patients with type 2 DM.     

Influence of apolipoprotein E genotype on the response to caloric restriction in type 2 diabetic patients with hyperlipidaemia

Aims:  Hyperlipidaemia is a major predisposing factor to atherosclerosis in patients with type 2 diabetes. Apolipoprotein (apo) E polymorphism influences lipoprotein metabolism, and the present study was undertaken to explore the relation, in type 2 diabetics, between apo E genotype and the plasma lipid response to dietary therapy.
Methods:  The subjects were 104 patients with type 2 diabetes and hyperlipidaemia, and the difference, due to apo E genotype, in dietary response was followed for 4–6 weeks. The caloric intake was maintained in the range 20–25 kcal/kg, and the medications for diabetes were not changed during the follow-up period.
Results:  Plasma total cholesterol (TC) and triglyceride (TG) levels were significantly lowered by the dietary treatment in patients with apo E genotypes of ε3/3, ε2/3 and ε3/4; however, the lipid levels in patients with ε2/4 did not respond to the diet.
Conclusions:  apo E genotype should be taken into consideration in the treatment of hyperlipidaemia in diabetic patients.     

Abnormalities in plasmas concentrations of lipoproteins and fibrinogen in Type 1 (insulin-dependent) diabetic patients with increased urinary albumin excretion

Summary Type 1 (insulin-dependent) diabetic patients with clinical nephropathy have a more than ten-fold increase in mortality of cardiovascular diseases compared with diabetic patients without nephropathy. The risk factors for cardiovascular disease, plasma concentrations of lipoproteins and fibrinogen, were investigated in 74 long-term diabetic patients: 37 with normal urinary albumin excretion, 20 with incipient nephropathy and 17 with overt clinical nephropathy based on urinary albumin excretion. The groups were matched according to sex, age and diabetes duration. The concentration of plasma cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride and fibrinogen rose with increasing urinary albumin excretion. The plasma concentrations of these lipoproteins and fibrinogen were 11–14% higher in the patients with incipient nephropathy and 26–87% higher in the patients with overt clinical ne phropathy compared with the patients without nephropathy. The plasma concentration of high density lipoprotein cholesterol was unaffected by albuminuria. Patients with normal urinary albumin excretion and HbA_1c>8.0% had significantly higher very low density lipoprotein- and lower high density lipoprotein cholesterol concentrations compared with patients with HbA_1c<8.0%. Simple addition of the described risk factors can only account for a minor part of the greatly increased cardiovascular mortality in patients with diabetic nephropathy. An additional and possibly more decisive factor might be a change in the arterial wall, a change which promotes lipid accumulation and/or facilitates thrombus formation.     

Acute reduction of arterial blood pressure reduces urinary albumin excretion in Type 1 (insulin-dependent) diabetic patients with incipient nephropathy

Summary The effect of an acute reduction in arterial blood pressure upon kidney function was studied in 12 patients with Type 1 (insulin-dependent) diabetes and incipient nephropathy (persistent microalbuminuria). Renal function was assessed by measurement of the glomerular filtration rate (single bolus ⁵¹Cr-EDTA technique) and by the urinary albumin excretion rate (radioimmunoassay). The study was performed twice within 2 weeks, with the patients receiving a slow intravenous injection of either clonidine (225 g) or saline (154 mmol/l) in random order. Clonidine reduced arterial blood pressure from 125/79±13/8 to 104/68±9/7 mmHg (p < 0.01), urinary albumin excretion rate from 68 (31–369) to 46 (6–200) g/min (median and range) (p<0.01), and fractional clearance of albumin in all patients (median 29%) (p < 0.01). Glomerular filtration rate was 110±11 before and 106±13 ml/min/1.73 m² after clonidine injection. The blood glucose concentration was 15±4mmol/l before and 14±5 mmol/l after clonidine injection. In agreement with findings in animal studies, our results suggest that microalbuminuria is to a large extent pressure-dependent, probably because of glomerular hypertension, and that autoregulation of glomerular filtration rate is normal in most patients with incipient diabetic nephropathy.     

Predominantly vegetarian diet in patients with incipient and early clinical diabetic nephropathy: effects on albumin excretion rate and nutritional status.

Several studies have suggested that dietary protein quality may be an important determinant in the natural history of renal disease. We have therefore studied the effects of a predominantly vegetarian diet in eight patients with Type 1 diabetes mellitus and an albumin excretion rate (AER) in excess of 30 micrograms min-1. The AER was measured after an 8-week run-in period on the patient's usual diet, and again after 8 weeks of a predominantly vegetarian diet in which the proportion of vegetable protein was supplemented in order to minimize the reduction in total dietary protein intake. The median fractional albumin clearance fell during the study from an initial value of 188 x 10(-+) (range 58-810 x 10(-4)) at the end of the run-in period to 87 x 10(-4) (23-829 x 10(-4)) at the end of the period on low animal protein diet (difference 79 x 10(-4) (95% Cl 9-149 x 10(-4)), p less than 0.05). The AER then returned to values similar to those obtained at the beginning of the study after a further 8 weeks in those patients returning to their usual diet. No significant changes in blood glucose control or in arterial pressure were observed. A predominantly vegetarian diet may therefore have important beneficial effects on diabetic nephropathy without the need for a heavily restricted total protein intake.     

Lecithin:cholesterol acyltransferase activity and high-density lipoprotein subfraction composition in type 1 diabetic patients with improving metabolic control

On initial diagnosis or when metabolic control is poor, subjects with type 1 (insulin-dependent) diabetes mellitus often exhibit decreased high density lipoprotein (HDL) cholesterol levels, which have been associated in numerous studies in non-diabetic subjects with atherosclerosis and coronary artery disease. We measured the activities of plasma lecithin:cholesterol acyltransferase (LCAT), post-heparin lipoprotein lipase, and the composition of the HDL subfractions HDL₂ and HDL₃, in ten poorly controlled type 1 diabetic patients admitted to a metabolic ward (six women and four men, aged 18–37 years). The measurements were repeated after metabolic control had been optimised and again a week after discharge. The results were compared with those of ten healthy normolipidaemic subjects matched for age, sex and body mass. LCAT activity increased significantly (P<0.05) with improved metabolic control in the diabetic patients, and showed positive within — person correlation with HDL₂ cholesterol ester (r=0.67;P<0.01), HDL₂ free cholesterol (r=0.67;P<0.01), phosphatidylcholine (r=0.49;P<0.05), total phospholipids (r=0.50;P<0.01) and apolipoprotein A-I (apo A-I:r=0.72;P<0.01). With improving metabolic control HDL₂ lipid levels increased more than twofold and the compositional changes in HDL₂ were reflected by an increased apo A-I:apo A-II ratio (P<0.05) and a decreased triglyceride:apo A-I ratio (P<0.05). Changes in HDL₃ levels and composition were minor. The results of this study indicate that an increase in LCAT activity increases the concentration and changes the composition of HDL₂ in type 1 diabetic patients with improved metabolic control.     

Long-term treatment with nifedipine reduces urinary albumin excretion and glomerular filtration rate in normotensive type 1 diabetic patients with microalbuminuria

The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria. In a randomized, double-blind trial, 15 type 1 diabetic patients were treated with either nifedipine (n=8; dosage 30 mg/day) or placebo (n=7) for 12 months. At baseline and after 6 and 12 months of therapy, the albumin excretion rate (UAER, radioimmunoassay), glomerular filtration rate (GFR, chromium 51 ethylenediamine tetra-acetic acid clearance) and renal plasma flow (RPF, iodine 125 hippuran clearance) were determined. Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months (median, Q₁/Q₃ in mg/24 h): baseline 84 (65/163); 6 months 35 (23/90),P<0.02; 12 months 39 (15/79),P<0.05. GFR was significantly decreased by nifedipine treatment (baseline 157±15, 6 months 122±8, 12 months 111±47 ml/min;P<0.05, mean ± SEM), whereas RPF remained constant. Nifedipine treatment did not influence systolic (baseline 121±7, 12 months 124±2 mmHg, mean ± SEM) or diastolic (baseline 72±2, 12 months 74±3 mmHg) arterial blood pressure. With placebo treatment no significant alterations of UAER, GFR, RPF and arterial blood pressure were observed. Metabolic control was constant throughout the whole study period. Thus, 1 year's treatment with nifedipine reduces the UAER and GFR in normotensive type 1 diabetic patients without influencing the systemic arterial blood pressure. The data, however, do not present a recommendation for the general use of nifedipine in these patients as the exact intrarenal mechanism of calcium channel blockers in humans remains to be established.     

First morning urinary albumin concentration is a good predictor of 24-hour urinary albumin excretion in children with Type I (insulin-dependent) diabetes

Summary Twenty-four hour urinary albumin excretion was measured in 97 children with Type 1 (insulin-dependent) diabetes and found to have a geometric mean of 6 mg/day (range 1–38 mg/d). The same geometric mean of 6 mg/day (range 1–45 mg/d) was found in 120 normal children. The relationship of 24-h urinary albumin excretion to the albumin concentration (mg/1) and to the ratio of albumin: creatinine (mg: mmol) on first morning urine samples in 64 patients was highly significant (r=0.93 and r=0.62 respectively, p < 0.001). In 41 patients, the relationship between 24-h urinary albumin excretion and albumin concentration upon urine samples at various times was assessed. The correlation was highest on the first morning sample (r=0.86); 09.00h to 13.00 h, 0.51; 13.00 h to 18.00 h, 0.68; 18.00 h to 23.00 h, 0.32. High sensitivity and moderate specificity was obtained using a first morning albumin concentration of greater than 20 mg/l to detect increased albumin excretion. These results show that the measurement of albumin concentration on the first morning urine sample can be used for a screening test for micro-albuminuria in children.     

Continuous subcutaneous insulin infusion is more effective than multiple daily insulin injections in preventing albumin excretion rate increase in Type 1 diabetic patients

Aims To compare the effect of continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) on albumin excretion rate (AER) in Type 1 diabetic patients. Methods In a 3‐year multicentre retrospective observational study, 110 Type 1 diabetic patients treated with CSII were compared with 110 patients treated with MDI matched at baseline for age, sex, diabetes duration and HbA_1c. At entry, 90 patients in each group had normal AER and 20 persistent microalbuminuria. AER, estimated glomerular filtration rate (eGFR), HbA_1c, lipids and blood pressure were assessed. Results HbA_1c was lower in the CSII than in the MDI group (8.1 ± 0.9 vs. 8.4 ± 1.3%; P < 0.005 after 3 years). Blood pressure and eGFR were similar during the study. AER [median (95% confidence interval)], similar at baseline [6.0 μg/min (9, 21) in the CSII group vs. 4.4 (8, 16) in the MDI group, NS] was significantly lower in the patients treated with CSII both at year 2 and at year 3 of follow‐up [4.7 μg/min (6, 12) vs. 6.4 (13, 29), P < 0.002]. This difference was observed even when normo‐ and microalbuminuric patients were analysed separately. Nine patients progressed to microalbuminuria in the MDI group and only one in the CSII group. Nine patients regressed to normoalbuminuria in the CSII group, whereas only two regressed to normoalbuminuria in the MDI group. Conclusions Despite a small benefit in terms of improved glycaemic control, CSII therapy may be useful in decreasing the progressive increase in AER in Type 1 diabetic patients.     

A promoter polymorphism in cholesterol 7alpha-hydroxylase interacts with apolipoprotein E genotype in the LDL-lowering response to atorvastatin

Bile-acid biosynthesis is a key determinant of intracellular cholesterol and, in turn, cholesterol synthesis rate in hepatocytes. This suggests that variation in the cholesterol 7alpha-hydroxylase gene (CYP7A1), a key enzyme in bile-acid biosynthesis, may influence the statin response. To test this hypothesis, a promoter polymorphism (A-204C) in CYP7A1 was examined in 324 hypercholesterolemic patients treated with atorvastatin 10mg. The variant C allele was significantly and independently associated with poor LDL cholesterol reductions; -39% in wild type allele homozygotes, -37% in variant allele heterozygotes, and -34% in variant allele homozygotes (p<0.0001 for trend). Differences were more striking in men, and were enhanced by the coexistence of common variants of apolipoprotein E gene (APOE), epsilon2 or epsilon4. In subjects having wild type alleles at both loci, the mean reduction in LDL cholesterol was -40%, while the value in subjects having two CYP7A1 variant alleles and at least one variant APOE allele was -31% (p<0.0001). Combination analysis of these two loci more accurately predicted the achievement of goal LDL cholesterol, than did both single locus analysis. We concluded that the CYP7A1 A-204C promoter variant was associated with poor response to atorvastatin, which were additively enhanced by common variants in another locus, APOE.     

Gender differences in a Type 2 (non-insulin-dependent) diabetic population with respect to apolipoprotein E phenotype frequencies

Summary Apolipoprotein E polymorphism was examined in an Italian population of Type 2 (non-insulin-dependent) diabetic patients. There were significant differences (p < 0.05) in allele frequencies between male and female patients due to an under-representation of the E4 allele in the female group. No differences in allele frequencies were noted when non-diabetic male and female control subjects were compared. Both control groups exhibited similar allele distributions to that of male diabetic patients, but were significantly different (p < 0.05) from female diabetic patients. A closer examination of the female diabetic population revealed that under-representation of the E4 allele was principally confined to patients aged 60 years or older. This sub-group showed a significantly different (p < 0.05) allele frequency profile from control subjects (both men and women) and diabetic men, whereas this was not observed in the younger diabetic women ( 59 years). The results are consistent with the suggestion that the E4 allele may be a particular risk factor for female diabetic patients.     

Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients.

AIMS: Elevated levels of urinary albumin excretion rate (AER) predict high risk for progressing to end-stage renal disease. In streptozotocin-induced diabetes, supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy. We tested the hypothesis that supplementation of both vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria. METHODS: Thirty Type 2 diabetic patients with AER 30-300 mg/24 h were included in a double-blind randomised, cross-over trial. Patients received vitamin C (1250 mg) and vitamin E (680 IU) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in random order. RESULTS: Combined treatment with vitamin C and E reduced AER by 19% (95% CI 6-34%) (p = 0.04), geometric mean 197 mg/24 h (95% CI 114-341 mg/24 h) vs. 243 mg/24 h (146-404 mg/24 h). No changes were seen in serum creatinine, haemoglobin A1C or blood pressure. Fasting plasma concentrations of vitamin C and E increased in all patients during active treatment (mean vitamin C 79.4 micromol/L (SD 27.8) vs. 41.9 micromol/L (18.4) and vitamin E 47.0 micromol/L (19.8) vs. 29.5 micromol/L (15.3), P < 0.000001). Except for two patients that started additional blood pressure lowering treatment during the run-in period, no changes in medication, food and exercise habits or in the number of smokers occurred during the study. CONCLUSION: Short-term treatment with vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with micro/macroalbuminuria. Further long-term, large-scale studies of this albuminuria reducing treatment modality are warranted.     

Changes in renal function in response to protein restricted diet in Type 1 (insulin-dependent) diabetic patients

Summary Glomerular filtration rate, renal plasma flow and urinary albumin excretion rate were measured during insulin-induced euglycaemia in 12 male Type 1 (insulin-dependent) diabetic patients after a 3-week period of low protein diet (45 g/day) or a similar period on unchanged conventional diet (103 g/day). No changes in glycaemic control, indicated by home blood glucose profiles and serum fractosamine concentration, or in arterial pressure, were noted on either diet. On low protein diet, glomerular filtration rate was lower (p<0.001) in all patients, but there was no difference in renal plasma flow between low protein diet and normal protein diet; filtration fraction fell significantly on low protein diet (p<0.001). Fractional clearance of albumin was also lower (p<0.05) on low protein diet. This study suggests that reduction of dietary protein induces, independently of changes in plasma glucose and arterial pressure, modifications in glomeralar filtration rate, filtration fraction and fractional clearance of albumin, which may be associated with a beneficial effect on the evolution of diabetic renal disease.     

Relationship between urinary excretion of sodium and dopamine in type 1 diabetic patients with an without microalbuminuria

The relationship between urinary sodium and dopamine excretion was investigated in 40 normal males and in 48 normotensive, Type 1 diabetic males, 11 with microalbuminuria and 37 with normal albumin excretion. In all three groups a significant correlation was demonstrated and the regression lines were similar. Thus, no evidence was found that a defect in dopamine mobilization contributes to the early renal pathophysiological changes of Type 1 diabetes.     

Unchanged incidence of severe retinopathy in a population of Type 1 diabetic patients with marked reduction of nephropathy

The incidence of nephropathy in Type 1 diabetes mellitus has declined during the past decade, probably as a result of improved glycaemic control. We wanted to investigate whether the incidence of severe retinopathy has changed during the same time period and to evaluate the importance of glycaemic control in relation to the development of severe retinopathy and nephropathy. All 213 patients in whom Type 1 diabetes mellitus was diagnosed before the age of 15 years between 1961 and 1980 in a district in south-eastern Sweden were studied. Ninety-two per cent of the patients were followed from the onset of diabetes to 1991 or to death. The cumulative incidence of severe retinopathy was not significantly different between the patients with diabetes onset 1961–65, 1966–70, 1971–75, and 1976–80. The risk of developing severe retinopathy or nephropathy was higher in patients with very poor glycaemic control (HbA_1c ≥ 8.4 %) vs patients with poor control (HbA_1c ≥ 7.2 < 8.4 %; p < 0.001). Patients with poor control had an increased risk of developing severe retinopathy vs patients with good control (HbA_1c < 7.2 %; p < 0.008) but there was no difference in the risk of nephropathy. No patients with good control developed nephropathy and only one patient developed severe retinopathy during 25 years of diabetes. © 1998 John Wiley & Sons, Ltd.     

Association between lipoprotein subfraction profile and the response to hepatitis C treatment in Japanese patients with genotype 1b

Summary. Pegylated interferon and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C (CHC). Some groups have reported a relation between lipid values and response while others have reported that microsomal triglyceride transfer protein, a key enzyme in the assembly and secretion of lipoproteins, was related to hepatitis C virus (HCV). The aim of this study was to investigate the association between the lipoprotein profiles, classified according to size, and hepatitis C treatment and the usefulness for predicting the outcome of treatment. Forty‐four patients with CHC (27 men and 17 women) were included in the study. The serum cholesterol and triglyceride (TG) levels in the lipoprotein subclasses were determined using high‐performance liquid chromatography with gel permeation columns, which classified lipoproteins into 20 subfractions based on particle size. According to a univariate analysis, those who achieved an sustained viral response (SVR) had a significantly higher serum total cholesterol level, higher cholesterol levels in the low‐density lipoprotein subfraction (25.5 nm in diameter) and the very low‐density lipoprotein (VLDL) subfraction (44.5 and 36.8 nm), and a higher serum TG level in the VLDL subfraction (44.5 nm), compared with the corresponding values in the non‐SVR group. Higher serum cholesterol and TG concentrations in the lipoprotein subfractions were predictive of an SVR to therapy for HCV infection with genotype 1b prior to the start of interferon treatment.     

Factors predicting the blood glucose lowering effect of a 30-day very low calorie diet in obese Type 2 diabetic patients.

OBJECTIVE: To identify factors which predict the blood glucose lowering effect of monotherapy with a 30-day very low calorie diet (VLCD) in obese Type 2 diabetic patients. A responder was a priori defined as a patient with a fasting plasma glucose (FPG) level < 10 mmol/l on day 30. RESEARCH DESIGN AND METHODS: In 17 obese patients (BMI 37.6 +/- 5.6 (mean +/- SD) kg/m(2)) with Type 2 diabetes, all blood glucose lowering medication (including insulin) was discontinued on day -1 followed by a 30-day VLCD. On day 2 and 30 of the VLCD an intravenous glucose tolerance test (IVGTT) was performed. RESULTS: Of the 14 patients who completed the 30-day VLCD, eight qualified as responder. Responders and non-responders could be distinguished by day 2. Responders had a shorter duration of Type 2 diabetes and higher fasting serum insulin, C-peptide and HOMA-beta-values. In addition, responders displayed a more prominent second-phase insulin response following i.v. glucose loading and higher k-values. In a stepwise discriminant analysis, the change in FPG from day 0 to day 2 (responders +0.64 +/- 2.3, non-responders +4.15 +/- 3.3 mmol/l, P = 0.035) in combination with the area under the curve of insulin (AUC) above baseline during an IVGTT on day 2 (responders 571 +/- 236, non-responders 88 +/- 65 mU*50 min, P < 0.001), distinguished responders completely from non-responders. CONCLUSION: Preservation of the capacity of beta-cells to secrete insulin predicts a favourable metabolic response to a VLCD in obese Type 2 diabetic patients.