Insulin autoimmune syndrome in an occidental woman: a case report and literature review

SUMMARY Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare hypoglycemic disorder characterized by spontaneous hypoglycemia associated with extremely high circulating insulin levels and positive anti-insulin antibody results. Thus far, most cases have been reported in Asian countries, notably Japan, with few cases reported in western countries. As a possible cause, it is associated with the use of drugs containing sulfhydryl radicals, such as captopril. This report refers to a 63-year-old female Brazilian patient with a history of postprandial hypoglycemia. After extensive investigation and exclusion of other causes, her hyperinsulinemic hypoglycemia was considered to have likely been induced by captopril. Most cases of IAS are self-limiting. However, dietary management, corticosteroids, plasmapheresis, and rituximab have already been used to treat patients with IAS. In our case, after discontinuation of captopril, an initial decrease in insulin autoantibody levels was observed followed by improvement in episodes of hypoglycemia. Although it is a rare disease, IAS should be considered in the differential diagnosis of endogenous hyperinsulinemic hypoglycemia. Patients with suspected IAS must be screened for autoimmunity-related drugs for insulin. Initial clinical suspicion of IAS can avoid unnecessary costs associated with imaging examinations and/or invasive surgical procedures.

Epidemiology and outcomes of hypoglycemia in patients with advanced diabetic kidney disease on dialysis: A national cohort study.

BACKGROUND: Patients with advanced diabetic kidney disease (DKD) behave differently to diabetic patients without kidney disease. We aimed to investigate the associations of hypoglycemia and outcomes after initiation of dialysis in patients with advanced DKD on dialysis. METHODS: Using National Health Insurance Research Database, 20,845 advanced DKD patients beginning long-term dialysis between 2002 and 2006 were enrolled. We investigated the incidence of severe hypoglycemia episodes before initiation of dialysis. Patients were followed from date of first dialysis to death, end of dialysis, or 2008. Main outcomes measured were all-cause mortality, myocardial infarction (MI), and subsequent severe hypoglycemic episodes after dialysis. RESULTS: 19.18% patients had at least one hypoglycemia episode during 1-year period before initiation of dialysis. Advanced DKD patients with higher adapted Diabetes Complications Severity Index (aDCSI) scores were associated with more frequent hypoglycemia (P for trend < 0.001). Mortality and subsequent severe hypoglycemia after dialysis both increased with number of hypoglycemic episodes. Compared to those who had no hypoglycemic episodes, those who had one had a 15% higher risk of death and a 2.3-fold higher risk of subsequent severe hypoglycemia. Those with two or more episodes had a 19% higher risk of death and a 3.9-fold higher risk of subsequent severe hypoglycemia. However, previous severe hypoglycemia was not correlated with risk of MI after dialysis. CONCLUSIONS: The rate of severe hypoglycemia was high in advanced DKD patients. Patients with higher aDCSI scores tended to have more hypoglycemic episodes. Hypoglycemic episodes were associated with subsequent hypoglycemia and mortality after initiation of dialysis. We studied the associations and further study is needed to establish cause. In addition, more attention is needed for hypoglycemia prevention in advanced DKD patients, especially for those at risk patients.

Hypoglycemia is common in children with cystic fibrosis and seen predominantly in females.

OBJECTIVE: To determine the prevalence of hypoglycemia in children and adolescents with cystic fibrosis (CF) in 2-hour oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) under free-living conditions. RESEARCH DESIGN AND METHODS: Height, weight, body mass index (BMI), hemoglobin A1c (HbA1c), and Forced expiratory volume (FEV1%) were measured in children with CF (aged 5-18 years). Following OGTT, CGM was installed for 3 days. The total hypoglycemic and hyperglycemic time (%) during 3 days was measured. Subjects were categorized according to hypoglycemic time <3% (hypo -) and ≥3% (hypo +). Each category was further divided according to hyperglycemic time <3% (hyper -) or ≥3% (hyper +). RESULTS: OGTT and CGM were sequentially performed in 45 CF patients. The frequency of hypoglycemia in OGTT and hypoglycemic time ≧3% of CGM were 13.3% and 27.5%, respectively. After 5 cystic fibrosis-related diabetes (CFRD) subjects were excluded, the number of subjects in each subgroup was 17 (hypo-/hyper-), 12 (hypo-/hyper+), 6 (hypo+/hyper-), and 5 (hypo+/hyper+). Significantly higher insulin at 120 minutes was observed in OGTT in (hypo+/hyper-), as compared with subgroup (hypo-/hyper-) (P = .018). Total insulin levels were also significantly higher in (hypo+/hyper-), than (hypo-/hyper-), but were similar to those in the healthy control group (P = .049 and P = .076, respectively). There was a female predominance in hypoglycemic subjects both in OGTT and subgroup (hypo+/hyper-) in the CGM group (P = .033 and P = .033, respectively). FEV1 was significantly lower in hypo + group as a whole, and (hypo+/hyper+) subgroup than in (hypo-/hyper-), (P = .044 and P = .042, respectively); the difference was independent of body mass index-standard deviation score (BMI-SDS) (P = .15 and P = .12, respectively). CONCLUSION: The frequency of hypoglycemia in children with CF was higher in CGM than that in OGTT. Insulin secretion was delayed and total insulin levels increased in the hypoglycemic patients. Glucose instability/hypoglycemia is associated with poorer lung function in patients with CF, independent of nutritional status.

Incretin-based drugs for type 2 diabetes: Focus on East Asian perspectives.

Type 2 diabetes in East Asians is characterized primarily by ß-cell dysfunction, and with less adiposity and less insulin resistance compared with that in Caucasians. Such pathophysiological differences can determine the appropriate therapeutics for the disease. Incretins, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are secreted in response to meal ingestion, and enhance insulin secretion glucose-dependently. Incretin-based drugs, dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists, that ameliorate ß-cell dysfunction with limited hypoglycemia risk are now widely used in type 2 diabetes management. Recent meta-analyses of clinical trials on DPP-4i and glucagon-like peptide-1 receptor agonists found that the drugs were more effective in Asians, most likely because of amelioration of ß-cell dysfunction. In addition, we found increased glycated hemoglobin-lowering effects of DPP-4i to be associated with intake of fish in type 2 diabetes, which suggests that dietary customs of East Asians might also underlie the greater efficacy of DPP-4i. Despite the limited risk, cases of severe hypoglycemia were reported for DPP-4i/sulfonylureas combinations. Importantly, hypoglycemia was more frequent in patients also receiving glibenclamide or glimepiride, which activate exchange protein directly activated by cyclic adenosine monophosphate 2, a critical mediator of incretin signaling, and was less frequent in patients receiving gliclazide, which does not activate exchange protein directly activated by cyclic adenosine monophosphate 2. Prevention of insulin-associated hypoglycemia by DPP-4i has gained attention with regard to the enhancement of hypoglycemia-induced glucagon secretion by insulinotropic polypeptide, but remains to be investigated in East Asians. Despite the safety issues, which are paramount and must be carefully monitored, the incretin-based drugs could have potential as a first choice therapy in East Asian type 2 diabetes patients.

Depression in Chinese patients with type 2 diabetes: associations with hyperglycemia, hypoglycemia, and poor treatment adherence.

BACKGROUND: We hypothesize that depression in type 2 diabetes might be associated with poor glycemic control, in part due to suboptimal self-care. We tested this hypothesis by examining the associations of depression with clinical and laboratory findings in a multicenter survey of Chinese type 2 diabetic patients. METHOD: 2538 patients aged 18-75 years attending hospital-based clinics in four cities in China underwent detailed clinical-psychological-behavioral assessment during a 12-month period between 2011 and 2012. Depression was diagnosed if Patient Health Questionnaire-9 (PHQ-9) score ≥10. Diabetes self-care and medication adherence were assessed using the Summary of Diabetes Self-care Activities and the 4-item Morisky medication adherence scale respectively. RESULTS: In this cross-sectional study (mean age: 56.4 ± 10.5[SD] years, 53% men), 6.1% (n = 155) had depression. After controlling for study sites, patients with depression had higher HbA(1c) (7.9 ± 2.0 vs. 7.7 ± 2.0%, P = 0.008) and were less likely to achieve HbA(1c) goal of <7.0% (36.2% vs 45.6%, P = 0.004) than those without depression. They were more likely to report hypoglycemia and to have fewer days of being adherent to their recommended diet, exercise, foot care and medication. In logistic regression, apart from young age, poor education, long disease duration, tobacco use, high body mass index, use of insulin, depression was independently associated with failure to attain HbA(1c) target (Odds Ratio [OR] = 1.56, 95%CI:1.05-2.32, P = 0.028). The association between depression and glycemic control became non-significant after inclusion of adherence to diet, exercise and medication (OR = 1.48, 95% CI 0.99-2.21, P = 0.058). CONCLUSION: Depression in type 2 diabetes was closely associated with hyperglycemia and hypoglycemia, which might be partly mediated through poor treatment adherence.

Clinical characteristics of people experiencing biochemical hypoglycaemia during an oral glucose tolerance test: cross-sectional analyses from a UK multi-ethnic population.

AIMS: People who experience biochemical hypoglycaemia during an oral glucose tolerance test (OGTT) may be insulin resistant, but this has not been investigated robustly, therefore we examined this in a population-based multi-ethnic UK study. METHODS: Cross-sectional data from 6478 diabetes-free participants (849 with fasting insulin data available) who had an OGTT in the ADDITION-Leicester screening study (2005-2009) were analysed. People with biochemical hypoglycaemia (2-h glucose <3.3mmol/l) were compared with people with normal glucose tolerance (NGT) or impaired glucose regulation (IGR) using regression methods. RESULTS: 359 participants (5.5%) had biochemical hypoglycaemia, 1079 (16.7%) IGR and 5040 (77.8%) NGT. Biochemical hypoglycaemia was associated with younger age (P<0.01), white European ethnicity (P<0.001), higher HDL cholesterol (P<0.01), higher insulin sensitivity (P<0.05), and lower body mass index (P<0.001), blood pressure (P<0.01), fasting glucose (P<0.001), HbA1C (P<0.01), and triglycerides (P<0.01) compared with NGT and IGR separately in both unadjusted and adjusted (age, sex, ethnicity, body mass index, smoking status) models. CONCLUSIONS: Biochemical hypoglycaemia during an OGTT in the absence of diabetes or IGR was not associated with insulin resistance, but instead appeared to be associated with more favourable glycaemic risk profiles than IGR and NGT. Thus, clinicians may not need to intervene due to biochemical hypoglycaemia on a 2-h OGTT.

A threefold increase in gestational diabetes over two years: review of screening practices and pregnancy outcomes in Indigenous women of Cape York, Australia.

BACKGROUND: Australian Aboriginal women have a high prevalence of type 2 diabetes (T2DM) in pregnancy and gestational diabetes (GDM). AIMS: To review how screening practice affects the pregnancy data of all Indigenous women and their newborns living in Cape York, Queensland. METHODS: All medical charts of mothers and their neonates delivered in the regional hospital over two-one-year periods (2006 and 2008) were reviewed. Universal testing with an oral glucose tolerance test (OGTT) was introduced in 2007. RESULTS: Gestational diabetes (GDM) increased from 4.7 to 14.2%, and T2DM was similar (2.4 and 2.3%). There were 127 deliveries in 2006 and 134 in 2008. Testing rates with OGTT improved from 31.4% in 2006 to 65.6% in 2008. Mothers with diabetes in pregnancy (DIP) were older and heavier than non-DIP mothers. Caesarean section rates were significantly higher in the DIP group compared with the non-DIP group (66 vs 25%) in both time periods. The booking weight of DIP mothers decreased 16 kg, their babies normalised their weight, length and head circumference; respiratory distress and Apgar scores improved comparing the two periods. In DIP, infants >40% had hypoglycaemia; however, rates of serious complications were low. Rates of breastfeeding were similar between groups. Follow-up rates for GDM improved from 16.6% in 2006 to 31.6% in 2008. Of those tested one-third were diagnosed with T2DM. CONCLUSION: The rate of GDM tripled after implementation of universal testing. Outcomes improved. There is still need for improvement in testing and follow-up practices in relation to DIP.