Michelle Fung

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.

Effect of exenatide on beta cell function after islet transplantation in type 1 diabetes.

Background. Islet transplantation can reduce or eliminate the need for insulin in patients with type 1 diabetes. Exenatide is a long acting analogue of Glucagon-like peptide-1 (GLP-1) that augments glucose induced insulin secretion, and may increase &bgr; cell mass. We evaluated the effect of exenatide on insulin secretion after islet transplantation. Methods. Eleven C-peptide positive islet cell recipients with elevated glucose levels were treated with exenatide for three months. Response was assessed by insulin requirements, meal tolerance tests, and hyperglycemic glucose clamps. Results. Ten patients responded to exenatide. Two patients who had not restarted insulin achieved good glycemic control and one patient who had received 5500 IE/kg in first islet infusion was able to stop insulin. Seven other patients decreased their insulin dose by 39% on exenatide. Hyperglycemic clamp studies showed a rise in second phase insulin release (before exenatide: 246±88 pM; during exenatide: 644±294 pM, P<0.01). Meal tolerance studies before and one month after stopping exenatide did not show a difference in glucose or C-peptide values. Nausea and vomiting were the major side effects. Conclusions. Exenatide stimulates insulin secretion in islet transplant recipients. It reduces insulin dose in some patients and may delay the need to resume insulin in others. We did not find any evidence of a trophic effect on islets.

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.

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 99mTc-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 m2) 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.

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.

Case series of type III hyperlipoproteinemia in children.

Type III hyperlipoproteinemia (type III HLP) rarely manifests in childhood. Long-term follow-up (37 years) of the first patient revealed hypothyroidism at diagnosis requiring thyroxine replacement, palmar xanthomas requiring surgical removal, splenomegaly requiring splenectomy, 18 episodes of pancreatitis and premature coronary artery disease. Investigation revealed an apolipoprotein E phenotype of E2/E2 and partial lipoprotein lipase deficiency. Investigation of the second patient revealed a combination of apoE2/E2 phenotype and heterozygous familial hypercholesterolaemia. The third patient had a complete deficiency of lipoprotein lipase activity, an abnormal thyroid stimulating hormone on diagnosis (with subsequent normalisation without treatment), and apoE2/E2 phenotype. Type III HLP is a serious disorder with lifelong consequences of premature vascular disease and recurrent pancreatitis. Early presentation of disease in our patients was associated with additional precipitating factors. Drug treatment of paediatric type III HLP is indicated if dietary modifications alone are insufficient in managing the dyslipidaemia.

A patient's informative mistake: niacin is very effective in correcting dyslipidaemia.

A 72-year-old man at high risk for cardiovascular disease, with a history of peripheral vascular disease and type 2 diabetes, presented with lipids above targets despite maximum daily treatment with atorvastatin 80 mg, fenofibrate supra 160 mg daily, and ezetimibe 10 mg. His low density lipoprotein cholesterol (LDL-C) was 2.6 mmol/l, total cholesterol: HDL ratio 5.6, and high density lipoprotein cholesterol (HDL-C) 0.9 mmol/l. Because his lipids were not within target, he was advised to start 2250 mg of niacin in three divided doses daily. For 5 months, he mistakenly took 2250 mg of niacin three times daily, a consumption of 6750 mg/day! The effects on his lipids were: HDL-C increased nearly 100% to 1.7 mmol/l, LDL-C decreased by 50% to 1.3 mmol/l, and cholesterol: HDL ratio decreased by over 50% to 2.1. His excessive intake dramatically demonstrates the positive effect of niacin on lipids. Fortunately he did not suffer adverse effects from taking more than the recommended limit of 3000 mg/day.

Patient Perceptions of Islet Transplantation for Type 1 Diabetes

ABSTRACT OBJECTIVE To determine the demand for islet transplantation among patients with type 1 diabetes. METHODS Surveys were mailed to patients with type 1 diabetes at 2 centres: 1 with an islet transplantation program (Vancouver, British Columbia) and another without a program (Halifax, Nova Scotia). The primary outcome was patient acceptance of islet transplantation after learning about the risks and benefits. RESULTS Of the 588 responses from a sample of 1499, 451 (76.7%) would accept or probably accept islet transplantation. Most common reasons for acceptance were 1) fewer diabetes-related complications (92.7%); 2) decreased hypoglycemia (78.5%); and 3) no insulin injections (75.0%). The rest, 137 (23.3%) respondents, would not or probably not accept islet transplantation because of 1) immunosuppressant medications (90.6%); 2) risks not yet identified (58.8%). Most would not consider islet transplantation a failure if insulin was required post-transplant (71%). Acceptance was higher among those who were younger and had less formal education and a lower household income. Patients who would accept islet transplantation had higher glycated hemoglobin, used higher doses of insulin and had worse perceived diabetes control and general health. CONCLUSIONS The majority of patients with type 1 diabetes surveyed for this study would accept islet transplantation, with expectations of fewer complications, decreased hypoglycemia and freedom from insulin.

To self-cite or not to self-cite

The article by Apoor Gami and associates[1][1] on self-citation in the diabetes literature included 1 self-citation (out of a total of 9 references), which involved 3 of the studys authors (reference 6 in the original article). Thus, self-citation constituted 11% of the articles citations, which