Reduced progression of diabetic retinopathy after islet cell transplantation compared with intensive medical therapy.

BACKGROUND: Diabetic retinopathy is a major complication of type 1 diabetes and remains a leading cause of visual loss. There have been no comparisons of the effectiveness of intensive medical therapy and islet cell transplantation on preventing progression of diabetic retinopathy. METHODS: The British Columbia islet transplant program is conducting a prospective, crossover study comparing medical therapy and islet cell transplantation on the progression of diabetic retinopathy. Progression was defined as the need for laser treatment or a one step worsening along the international disease severity scale. An interim data analysis was performed after a mean 36-month follow-up postislet transplantation and these results are presented. RESULTS: The medical and postislet transplant groups were similar at baseline. Subjects after islet transplantation had better glucose control than the medically treated subjects (mean HbA1c 6.7%+/-0.9% vs. 7.5+/-1.2, P<0.01) and were C-peptide positive. Progression occurred significantly more often in all subjects in the medical group (10/82 eyes, 12.2%) than after islet transplantation (0/51 eyes, 0%) (P<0.01). Considering only subjects who have received transplants, progression occurred in 6/51 eyes while on medical treatment and 0/51 posttransplant (P<0.02). CONCLUSIONS: Progression of diabetic retinopathy was more likely to occur during medical therapy than after islet cell transplantation.

The effect of medical therapy and islet cell transplantation on diabetic nephropathy: an interim report.

BACKGROUND: The effect of islet cell transplantation (ICT) on renal function in type 1 diabetes is uncertain and some recent studies report a significant decline in estimated glomerular filtration rate (GFR) and worsening of albuminuria. METHODS: We are conducting a prospective crossover study comparing medical treatment with islet transplantation on the progression of diabetic complications, including renal function. The primary endpoint is change in GFR measured by Tc-diethylenetriaminepentaacetate with secondary endpoints including estimated GFR and albumin excretion. RESULTS: We have followed 21 patients after islet transplantation a median of 29 months (range 13-45) and compared their results with medically treated patients followed a median 29.5 months (range 13-56). There is no difference in the rate of decline in measured GFR between medically treated patients (-0.35+/-0.89; 95% CI: -0.57 to -0.13 mL/min/month/1.73 m) and those after ICT (-0.31+/-1.18; 95% CI: -0.61 to -0.01) and neither is significantly different from that expected for the general population. The rate of decline in our estimated GFR results is lower than that reported in other studies and we did not find any worsening of albuminuria. CONCLUSIONS: We do not find evidence of worsening of renal function after islet transplantation compared with medically treated patients.

Addition of pioglitazone or bedtime insulin to maximal doses of sulfonylurea and metformin in type 2 diabetes patients with poor glucose control: a prospective, randomized trial.

PURPOSE: To compare the efficacy of adding pioglitazone or bedtime isophane (NPH) insulin to maximal doses of metformin and an insulin secretagogue in patients with poor glucose control. METHODS: We conducted a nonblinded, open-label, randomized controlled trial involving 62 patients with type 2 diabetes and glycosylated hemoglobin (HbA1C) levels >8.0%. Patients received either pioglitazone or bedtime NPH insulin in addition to their usual diabetes medication for 16 weeks. Outcome measurements of glycemic control, hypoglycemia, blood pressure, lipid levels, microalbuminuria, and quality of life were assessed at baseline and at 16 weeks. RESULTS: HbA1C levels were lowered to a similar degree in each treatment arm (pioglitazone: -1.9% +/- 1.5%; insulin: -2.3% +/- 1.5%; P = 0.32), but hypoglycemia was less common among patients who received pioglitazone than those who received insulin (37% [11/30] vs. 68% [19/28], P=0.02). Pioglitazone, but not insulin, resulted in an increase in high-density lipoprotein (HDL) cholesterol levels. Both treatments had similar effects on weight, other lipid values, blood pressure, and urine microalbumin levels. CONCLUSION: Adding pioglitazone or bedtime insulin for 16 weeks improved glycemic control in type 2 diabetic patients with secondary oral agent failure. Pioglitazone was associated with less hypoglycemia and improved HDL cholesterol levels.

Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy.

BACKGROUND: The effect of islet cell transplantation (ICT) on the progression of diabetic microvascular complications is not well understood. METHODS: We have conducted a prospective, crossover, cohort study comparing ICT with intensive medical therapy on the progression of diabetic nephropathy, retinopathy, and neuropathy. RESULTS: The rate of decline in glomerular filtration rate is slower after ICT than on medical therapy. There was significantly more progression of retinopathy in medically treated patients than post-ICT. There was a nonsignificant trend for improved nerve conduction velocity post-ICT. CONCLUSIONS: ICT is associated with less progression of microvascular complications than intensive medical therapy. Multicenter, randomized trials are needed to further study the role of ICT in slowing the progression of diabetic complications.

A multi-year analysis of islet transplantation compared with intensive medical therapy on progression of complications in type 1 diabetes.

BACKGROUND: We hypothesized that transplantation of islets into type 1 diabetics could improve outcomes of glucose metabolism, renal function, retinopathy, and neuropathy compared with intensive medical therapy. METHODS: We conducted a prospective, crossover, cohort study of intensive medical therapy (group 1) versus islet cell transplantation (group 2) in 42 patients. All were enrolled in group 1 then 31 crossed over with group 2 when islet donation became available. Transplantation was performed by portal venous embolization of more than 12,000 islet equivalents/kg body weight under cover of immunosuppression with antithymocyte globulin, tacrolimus, and mycophenolate. Outcome measures were HbA1c, change in glomerular filtration rate (GFR), progression of retinopathy, and change in nerve conduction velocity. This report details interim analysis of outcomes after 34+/-18 months (group 1) and 38+/-18 months (group 2). RESULTS: HbA1c (%) in group 1 was 7.5+/-0.9 versus 6.6+/-0.7 in group 2 (P<0.01). GFR (mL/min/month) declined in both groups (group 1 -0.45+/-0.7 vs. group 2 -0.12+/-0.7, P=0.1). Slope of the GFR decline in group 1 was significantly more than 0. Retinopathy progressed in 10 of 82 eyes in group 1 versus 0 of 51 in group 2 (P<0.01). Nerve conduction velocity (m/sec) remained stable in group 1 (47.8+/-5 to 47.1+/-5 m/sec) and group 2 (47.2+/-4.5 to 47.7+/-3.5). CONCLUSION: Islet transplantation yields improved HbA1c and less progression of retinopathy compared with intensive medical therapy during 3 years follow-up.

Normal perinatal mortality in type 1 diabetes mellitus in a series of 300 consecutive pregnancy outcomes.

Reports of outcomes of pregnancy in women with type 1 diabetes have consistently found increased perinatal mortality and morbidity. The primary objective of our study was to compare the perinatal mortality rate in type 1 diabetic pregnancies with that of the general population. The secondary objective was to compare the morbidities in these groups. A series of 247 women with type 1 diabetes had 300 consecutive pregnancy outcomes analyzed over a 10-year period. They were compared with the control population from the same hospital. Perinatal mortality was 6.6/1000 (95% CI, 0-17), which was significantly lower than the control population rate of 31/1000. There was an increased incidence of morbidity including maternal hypertension, cesarean section, preterm delivery, birth injury, large for gestational age infants, admissions to neonatal intensive care, neonatal hypoglycemia, and phototherapy. Pregnancies in type 1 diabetes can be associated with a normal perinatal mortality rate although morbidity remains elevated compared with controls.