Insulin allergy: a diagnostic and therapeutic strategy based on a retrospective cohort and a case-control study.

AIMS/HYPOTHESIS: Insulin allergy is a rare but significant clinical challenge. We aimed to develop a management workflow by (1) validating clinical criteria to guide diagnosis, based on a retrospective cohort, and (2) assessing the diagnostic performance of confirmatory tests, based on a case-control study. METHODS: In the retrospective cohort, patients with suspected insulin allergy were classified into three likelihood categories according to the presence of all (likely insulin allergy; 26/52, 50%), some (possible insulin allergy; 9/52, 17%) or none (unlikely insulin allergy; 17/52, 33%) of four clinical criteria: (1) recurrent local or systemic immediate or delayed hypersensitivity reactions; (2) reactions elicited by each injection; (3) reactions centred on the injection sites; and (4) reactions observed by the investigator (i.e. in response to an insulin challenge test). All underwent intradermal reaction (IDR) tests. A subsequent case-control study assessed the diagnostic performance of IDR, skin prick and serum anti-insulin IgE tests in ten clinically diagnosed insulin allergy patients, 24 insulin-treated non-allergic patients and 21 insulin-naive patients. RESULTS: In the retrospective cohort, an IDR test validated the clinical diagnosis in 24/26 (92%), 3/9 (33%) and 0/14 (0%) likely, possible and unlikely insulin allergy patients, respectively. In the case-control study, an IDR test was 80% sensitive and 100% specific and identified the index insulin(s). The skin prick and IgE tests had a marginal diagnostic value. Patients with IDR-confirmed insulin allergy were treated using a stepwise strategy. CONCLUSIONS/INTERPRETATION: Subject to validation, clinical likelihood criteria can effectively guide diabetologists towards an insulin allergy diagnosis before undertaking allergology tests. An IDR test shows the best diagnostic performance. A progressive management strategy can subsequently be implemented. Continuous subcutaneous insulin infusion is ultimately required in most patients. CLINICALTRIALS: gov: NCT01407640.

Low glycemic index foods should play a role in improving overall glycemic control in type-1 and type-2 diabetic patients and, more specifically, in correcting excessive postprandial hyperglycemia.

There is a large bulk of evidence that using low glycemic index (GI) foods has a very significant impact on the amelioration of metabolic disturbances observed in diabetic and/or hyperlipidemic patients and in subjects affected by the metabolic syndrome. Studies bringing convincing evidence against this concept are very rare if any. Improvement is observed not only in postprandial blood glucose and insulin variations but also in circulating plasma lipid levels and the morphology and function of adipocytes. Using the concept of low GI foods in diet counseling of diabetic patients is not exclusive of other measures to improve postprandial and overall blood glucose control. On the contrary, the use of low GI foods should be considered as one of other means and tools available to improve diabetes control (such as other dietary modifications, use of specific and nonspecific drug therapy altering postprandial blood glucose). Among these therapies, the most promising ones are alpha-glucosidase inhibitors, glynides, rapid insulin analogues and in the near future the GLP1 analogue. Again, all these classes of drugs could be associated with one another in order to obtain a postprandial delta excursion target of not below 20 and not above 40-50 mg/dl blood glucose.

The T-786C and C774T endothelial nitric oxide synthase gene polymorphisms independently affect the onset pattern of severe diabetic retinopathy.

Genetic factors could be implicated in the pathogenesis of severe diabetic retinopathy (DR). Recently, we reported a strong association between the eNOS4b/a endothelial nitric oxide synthase (eNOS) polymorphism and severe DR. To examine whether T-786C and C774T eNOS polymorphisms are involved in severe DR, 254 Caucasians with longstanding C-peptide-negative type 1 diabetes, 128 patients with absent/mild DR (control group), and 126 patients with preproliferative/proliferative DR (study group) were genotyped. The distribution of T-786C and C774T eNOS polymorphisms was in Hardy-Weinberg equilibrium and did not differ between the study and control groups. However, in case patients (n=126), T-786C and C774T polymorphisms influenced the onset pattern of severe DR (P=0.0169 and P=0.0257, respectively). The C-786C genotype was associated with early-onset severe DR (duration of diabetes: 15.2+/-5.9 vs. 19.4+/-6.3 years, P=0.0105), and the homozygous T774T genotype was associated with late-onset severe DR (24.3+/-7.0 vs. 18.4+/-6.2 years, P=0.0067). In the case of patients with high glycosylated hemoglobin levels (HbA1c >8%, n=88), the association between the T-786C polymorphism and early-onset severe DR was stronger (P=0.0068). Case patients carrying the C-786C genotype had higher HbA1c values (9.61+/-1.89%) than those carrying the T-786T genotype (8.93+/-1.47%, P=0.0173). Multivariate analysis showed that T-786C polymorphism was the best independent factor for onset pattern of severe DR (P<0.001). These findings, supported by previous associations between eNOS4b/a polymorphism and DR, suggest that T-786C and C774T eNOS polymorphisms affect the onset pattern of severe DR.

Improved plasma glucose control, whole-body glucose utilization, and lipid profile on a low-glycemic index diet in type 2 diabetic men: a randomized controlled trial.

OBJECTIVE: To determine whether a chronic low-glycemic index (LGI) diet, compared with a high-glycemic index (HGI) diet, has beneficial effects on plasma glucose control, lipid metabolism, total fat mass, and insulin resistance in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Twelve type 2 diabetic men were randomly allocated to two periods of 4 weeks of an LGI or HGI carbohydrate diet separated by a 4-week washout interval, in a crossover design. RESULTS: The LGI diet induced lower postprandial plasma glucose and insulin profiles and areas under the curve than after the HGI diet. At the end of the two dietary periods, the 7-day dietary records demonstrated equal daily total energy and macronutrient intake. Body weight and total fat mass were comparable. Four-week LGI versus HGI diet induced improvement of fasting plasma glucose (P < 0.01, Delta changes during LGI vs. HGI), HbA(1c) (P < 0.01), and whole-body glucose utilization measured by the euglycemic-hyperinsulinemic clamp (P < 0.05). LGI diet induced a decrease in fasting plasma total and LDL cholesterol (Delta changes LGI vs. HGI, P < 0.01), free fatty acids (P < 0.01), apolipoprotein B, and plasminogen activator inhibitor 1 activity. CONCLUSIONS: Only 4 weeks of an LGI diet was able to improve glycemic control, glucose utilization, some lipid profiles, and the capacity for fibrinolysis in type 2 diabetes. Even if changes in glycemic control were modest during the 4-week period, the use of an LGI diet in a longer-term manner might play an important role in the treatment and prevention of diabetes and related disorders.