Israel Medical Association Journal

Background: Type 2 diabetes mellitus is a multifactorial disease in which genetic susceptibility and environmental factors induce pancreatic β-cell dysfunction and insulin resistance. Additional factors such as hyperglycemia and hyperlipidemia have roles in β-cell dysfunction and disease progression. The phenomenon of lipid-induced pancreatic β-dysfunction, designated as lipotoxicity, has been observed in several in vitro and in vivo experiments; however, there is still no solid evidence for the occurrence of this event in humans. The toxic effect of high lipid levels on β-cell function consists of impaired insulin gene expression, apoptosis, and reduced glucose-stimulated insulin secretion.

Objectives: To demonstrate the importance of treating hypertriglyceridemia in reducing glucose intolerance and the need for insulin therapy in hospitalized diabetic patients.

Methods: We evaluated five clinical case reports and conducted a detailed literature review via the PubMed search engine.

Results: Reduction in elevated blood triglyceride and glucose levels in hospitalized diabetic patients resulted in a rapid decline in glucose levels and in the need for insulin therapy.

Conclusions: A decrease in high triglyceride levels in “lipotoxic” diabetic patients may improve insulin intolerance and glucose homeostasis and reduce the need for insulin therapy.

Background: Diabetic ketoacidosis (DKA) as the first presentation of type 1 diabetes mellitus (T1DM) is a serious complication that is preventable.

Objectives: To identify risk factors for DKA at presentation of T1DM to delineate high-risk Israeli populations that could benefit from preventative measures.

Methods: Data for this multicenter retrospective study were collected from the medical files of three pediatric diabetes centers representing three districts in Israel. Inclusion criteria were diagnosis of T1DM, age at diagnosis ≤ 17 years, permanent residency in Israel, and documentation of the presence or absence of DKA at presentation.

Results: The study population included 607 patients of whom 438 met the inclusion criteria. The mean age at diagnosis was 9.1 ± 4.5 years. DKA was present at diagnosis in 156/438 patients (35.6%). The incidence of DKA was different among the three diabetes centers (P = 0.04). The DKA group was significantly younger than the non-DKA group (8.4 ± 4.5 vs. 9.5 ± 4.4, respectively, P = 0.008). DKA was significantly associated with maternal origin (Ashkenazi Jewish origin [lower] vs. non-Ashkenazi, P = 0.04) and with paternal education level (academic [lower] vs. non-academic education, P = 0.04). Stepwise logistic regression showed that maternal Ashkenazi Jewish origin has a protective effect on DKA (odds ratio [OR] 0.4, 95% confidence interval [95%CI] 0.21–0.74, P = 0.004) and that younger age is an independent risk factor (OR 1.06, 95%CI 1.01–1.1, P = 0.02).

Conclusions: A diabetes educational program targeting high-risk population groups may reduce the prevalence of DKA nationwide.

Background: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive.

Objectives: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward.

Methods: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function.

Results: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis.

Conclusions: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.

Background: Patients with type 1 diabetes (T1D) are exempt from conscript military service, but some volunteer for national service. 

Objectives: To evaluate the effect of national service (military or civil) on metabolic control and incidence of acute diabetes complications in young adults with T1D. 

Methods: Clinical and laboratory data of 145 T1D patients were retrieved from medical records. The cohort comprised 76 patients volunteering for national service and 69 non-volunteers. Outcome measures were HbA1c, body mass index-standard deviation scores (BMI-SDS), insulin dosage, and occurrence of severe hypoglycemia or diabetic ketoacidosis (DKA). 

Results: Metabolic control was similar in volunteers and non-volunteers: mean HbA1c at various time points was: 7.83 ± 1.52% vs. 8.07% ± 1.63 one year before enlistment age, 7.89 ± 1.36% vs. 7.93 ± 1.42% at enlistment age, 7.81 ± 1.28% vs. 8.00 ± 1.22% one year thereafter, 7.68 ± 0.88% vs. 7.82 ± 1.33% two years thereafter, and 7.62 ± 0.80% vs. 7.79 ± 1.19% three years thereafter. There were no significant changes in HbA1c from baseline throughout follow-up. BMI and insulin requirements were similar and remained unchanged in volunteers and controls: mean BMI-SDS one year before enlistment age was 0.23 ± 0.83 vs. 0.29 ± 0.95, at enlistment age 0.19 ± 0.87 vs. 0.25 ± 0.98, one year thereafter 0.25 ± 0.82 vs. 0.20 ± 0.96, two years thereafter 0.10 ± 0.86 vs. 0.15 ± 0.94, and three years thereafter 0.20 ± 0.87 vs. 0.16 ± 0.96. Mean insulin dose in U/kg/day one year before enlistment age was 0.90 ± 0.23 vs. 0.90 ± 0.37, at enlistment age 0.90 ± 0.28 vs. 0.93 ± 0.33, one year thereafter 0.86 ± 0.24 vs. 0.95 ± 0.33, two years thereafter 0.86 ± 0.21 vs. 0.86 ± 0.29, and three years thereafter 0.87 ± 0.23 vs. 0.86 ± 0.28. There were no episodes of severe hypoglycemia or DKA in either group. 

Conclusions: Our data indicate that during voluntary national service young adults with T1D maintain metabolic control similar to that of non-volunteers. 

 

Background: Helicobacter pylori (HP) infection of the gastric mucosa may be involved in the development of insulin resistance (IR). 

Objectives: To investigate the association between HP status in stomach biopsies and weight reduction in patients who underwent laparoscopic sleeve gastrectomy (LSG). 

Methods: In this retrospective analysis of medical charts, all patients who underwent LSG for weight reduction and had at least 1 year of follow-up were included. HP status was ascertained by two to four biopsies of the removed stomach. 

Results: The study group comprised 70 patients; their mean age was 45.9 ± 11.9 years and 31.9% were males. Fourteen patients (20%) tested positive for HP colonization in gastric mucosa. HP status was not associated with age or smoking status. No difference was noted in the rate of diabetes mellitus (DM) or hypertension, but patients with HP had lower rates of hyperlipidemia (0 vs. 29 patients, 52%, P < 0.001). Patients lost an average of 10.5 kg/m2 after 12 months of follow-up, and no difference was noted between HP-positive and HP-negative patients. The rate of DM control was also similar between HP-positive and HP-negative patients at baseline (33.3 vs. 29.4, P = NS) and at 12 months of follow-up (70% vs. 50%, P = NS). 

Conclusions: HP status was not associated with changes in metabolic profiles and co-morbidity status, or in the efficacy of LSG. 

 

Background: Proteinuria and albuminuria are markers of kidney injury and function, serving as a screening test as well as a means of assessing the degree of kidney injury and risk for cardiovascular disease and death in both the diabetic and the non-diabetic general population.

Objectives: To evaluate the association between proteinuria below 300 mg/24 hours and albuminuria, as well as a possible association with kidney function in patients with diabetes mellitus (DM).

Methods: The medical files of patients with type 1 and type 2 DM with proteinuria below 300 mg/24 hours at three different visits to the Diabetic Nephropathy Clinic were screened. This involved 245 patient files and 723 visits. The data collected included demographics; protein, albumin and creatinine levels in urine collections; blood biochemistry; and clinical and treatment data. 

Results: The association between proteinuria and albuminuria is non-linear. However, proteinuria in the range of 162–300 mg/24 hours was found to be linearly and significantly correlated to albuminuria (P < 0.001, r = 0.58). Proteinuria cutoff, based on albuminuria cutoff of 30 mg/24 hours, was found to be 160.5 mg/24 hr. Body mass index (BMI) was the sole independent predictor of proteinuria above 160.5 mg/24 hr. Changes in albuminuria, but not proteinuria, were associated with changes in creatinine clearance. 

Conclusions: A new cutoff value of 160.5 mg/hr was set empirically, for the first time, for abnormal proteinuria in diabetic patients. It appears that proteinuria below 300 mg/24 hr is not sufficient as a sole prognostic factor for kidney failure. 

 

Background: Diabetes mellitus (DM) is a metabolic sequel in people infected with HIV, especially following the advent of HAART. This may be a particular concern in immigrants due to lifestyle changes. 

Objectives: To characterize the prevalence of DM in HIV-infected Ethiopians in Israel, and to define the risk factors.

Methods: We retrospectively screened the records of 173 HIV-infected Ethiopians and 69 HIV-infected non-Ethiopian HIV patients currently registered at the HIV Clinic of Meir Medical Center. Data were also retrieved from 1323 non-HIV Ethiopians treated in the hospital between 2007 and 2012. The presence of DM was determined by family physician diagnosis as recorded in the hospital database or by the presence of one or more of the following: fasting glucose > 127 mg/dl, hA1C > 6.5% (> 48 mmol/mol), or blood glucose > 200 mg/dl. Population data and risk factors for DM were analyzed by univariate and multivariate analyses. 

Results: Among HIV-infected Ethiopian subjects, the prevalence of DM was 31% (54/173) compared to 4% (3/69) in HIV-infected non-Ethiopians and 8% (102/1323) in non-HIV-infected Ethiopians (P < 0.0001). The relatively increased prevalence of DM was age independent, but most noticeable in those under the median age (< 42 years). Body mass index (BMI) was a predictor for DM (OR 1.263, CI 1.104–1.444, P = 0.001), although its values did not vary between the two ethnic groups. 

Conclusions: HIV-infected Ethiopians are more likely to develop DM at low BMI values compared to non-Ethiopians. This observation questions the relevance of accepted BMI values in this population and suggests that preventive measures against DM be routinely taken in these subjects. 

 

Background: Admission glucose levels correlate with clinical outcome in patients with type 2 diabetes mellitus (T2DM) hospitalized in general medicine wards. 

Objective: To investigate whether in-hospital hyperglycemia alone and after adjustment for age, gender and lipidemia correlates with in- and out-of-hospital mortality.

Methods: Capillary glucose, serum lipids and diagnoses at discharge among patients with T2DM hospitalized in the general medical wards of our hospital were documented. Correlation with in- and out-of-hospital mortality was determined through uni- and multivariate analyses. 

Results: Of the 4607 patients included in the study 22% died while hospitalized. From a median of five capillary glucose tests obtained per patient, average capillary glucose level was significantly lower in those who survived than in those who died (174 ± 64 vs. 180 ± 65 mg/dl, P = 0.005). Overall, blood cholesterol was higher in those who survived than in those who died (P < 0.001). Multivariate analysis, however, including age, gender, lipidemia and glycemia, showed that only age and male gender correlated with mortality.

Conclusions: Hyperglycemia was associated with increased in- and out-of-hospital mortality on univariate analysis. However, it was not an independent risk factor when corrected for age, gender and hyperlipidemia. 

 

Abstract

Background: The impact of admission glycated hemoglobin (HbA1c) on hospital outcome is controversial.

Objectives: To evaluate the association between admission glucose and HbA1c levels and mortality 1 year after hospitalization in the internal medicine ward.

Methods: HbA1c level of consecutive patients was measured during the first 24 hours of admission to the internal medicine ward and divided at the cutoff point of 6.5%. Three groups of patients were prospectively identified: patients with preexisting diabetes mellitus (DM), patients with glucose > 140 mg/dl (hyperglycemia) on admission and no known diabetes (H), and patients without diabetes or hyperglycemia (NDM). The primary end-point was 1 year all-cause mortality.

Results: A total of 1024 patients were enrolled, 592 (57.8%) belonged to the DM group, 119 (11.6%) to the H group and 313 (30.6%) to the NDM group. At 1 year, death occurred in 70 (11.9%) in the DM group, 12 (10.0%) in the H group and 15 (4.8%) in the NDM group (P = 0.002). Elevated admission glucose levels did not influence outcome in any of the groups. HbA1c levels were similar for survivors and non-survivors (P = 0.60). Within-group multivariate analysis adjusted for comorbidities and age showed that in the H group HbA1C levels of 6.5% or above were associated with increased mortality risk [hazard ratio (HR) 8.25, 95% confidence interval (CI) 1.93–35.21). In the DM group, HbA1c levels below 6.5% were associated with increased mortality risk (HR = 2.05, 95%CI 1.25–3.36).

Conclusions: Glucose levels upon admission did not affect mortality. However, HbA1c levels below 6.5% had opposite effects on 1 year mortality in diabetes patients and patients with hyperglycemia.

Background: While earlier studies indicated that cholesterol levels decrease significantly after an acute myocardial infarction (MI), a more recent study refuted this observation. 

Objectives: To assess changes in plasma lipid levels after onset of acute MI, and determine important predictors of lipid dynamics.

Methods: We prospectively measured lipid levels of patients who presented with an acute MI. Blood samples were drawn on admission to the hospital (day 1), after fasting at least 12 hours overnight (day 2), and on the 4th day of hospitalization (day 4). 

Results: Of 67 acute MI patients, 30 were admitted for ST elevation MI (STEMI) and 37 for non-STEMI. Both total cholesterol and low density lipoprotein cholesterol (LDL-C) levels decreased significantly (by 9%) in the 24 hours after admission and by 13% and 17% respectively on day 4. High density lipoprotein cholesterol (HDL-C) levels as well as triglycerides did not change significantly. Independent predictors of LDL-C decrease were the presence of diabetes mellitus [odds ratio (OR) 6.73, P = 0.01), and elevated cardiac troponin T (cTnT) levels (OR 1.81, P < 0.04).

Conclusions: LDL-C levels decrease significantly after an acute MI. The reduction is correlated with cTnT levels. Diabetes is a strong independent predictor of LDL-C decrease. In acute MI patients only measurements taken within 24 hours of onset should be used to guide selection of lipid-lowering medication.