ANALYSIS OF CLINICAL AND LABORATORY PARAMETERS CHILDREN WITH DIABETES MELLIUS TYPE 1 USING DIFFERENT TYPES OF INSULIN PREPARATIONS.

A comparative analysis of clinical and laboratory parameters was carried out in 49 children. The patients were divided into 3 groups depending on the type of insulin they received. Group 1 included 20 children who used Insulin human (Insulatard), group 2 included 15 children using insulin Glargine, and group 3 included 14 children using insulin Detemir. All children using Detemir and Glargine used short acting insulin Aspart. Those using Insulin human (Insulatard) used Human insulin (rDNA, Actrapid) in addition. In all children, blood glucose, glycohemoglobin and cholesterol were determined by laboratory methods. Statistical calculations were carried out using a statistical package at a confidence level of p＜0.05. A significant difference was found between the mean values of glycohemoglobin and glucose of Glargine users and patients with using Insulin human (Insulatard) (p≺0.05). These indicators were lower in Glargine users. There is a positive correlation between doses of Regular insulin and Insulin human (Insulatard) with body weight and height. There is a positive correlation between dose of Detemir and body mass. However, no such relationship between Glargine, body mass and height was recorded. It was a negative correlation between its dose Glargine with glycohemoglobin and also between glucose and cholesterol using Glargine.

Insulin Sensitization Following a Single Exercise Bout Is Uncoupled to Glycogen in Human Skeletal Muscle: A Meta-analysis of 13 Single-Center Human Studies.

Exercise profoundly influences glycemic control by enhancing muscle insulin sensitivity, thus promoting glucometabolic health. While prior glycogen breakdown so far has been deemed integral for muscle insulin sensitivity to be potentiated by exercise, the mechanisms underlying this phenomenon remain enigmatic. We have combined original data from 13 of our studies that investigated insulin action in skeletal muscle either under rested conditions or following a bout of one-legged knee extensor exercise in healthy young male individuals (n = 106). Insulin-stimulated glucose uptake was potentiated and occurred substantially faster in the prior contracted muscles. In this otherwise homogenous group of individuals, a remarkable biological diversity in the glucometabolic responses to insulin is apparent both in skeletal muscle and at the whole-body level. In contrast to the prevailing concept, our analyses reveal that insulin-stimulated muscle glucose uptake and the potentiation thereof by exercise are not associated with muscle glycogen synthase activity, muscle glycogen content, or degree of glycogen utilization during the preceding exercise bout. Our data further suggest that the phenomenon of improved insulin sensitivity in prior contracted muscle is not regulated in a homeostatic feedback manner from glycogen. Instead, we put forward the idea that this phenomenon is regulated by cellular allostatic mechanisms that elevate the muscle glycogen storage set point and enhance insulin sensitivity to promote the uptake of glucose toward faster glycogen resynthesis without development of glucose overload/toxicity or feedback inhibition.

Exploring Visceral and Subcutaneous Adipose Tissue Secretomes in Human Obesity: Implications for Metabolic Disease.

Adipose tissue secretions are depot-specific and vary based on anatomical location. Considerable attention has been focused on visceral (VAT) and subcutaneous (SAT) adipose tissue with regard to metabolic disease, yet our knowledge of the secretome from these depots is incomplete. We conducted a comprehensive analysis of VAT and SAT secretomes in the context of metabolic function. Conditioned media generated using SAT and VAT explants from individuals with obesity were analyzed using proteomics, mass spectrometry, and multiplex assays. Conditioned media were administered in vitro to rat hepatocytes and myotubes to assess the functional impact of adipose tissue signaling on insulin responsiveness. VAT secreted more cytokines (IL-12p70, IL-13, TNF-α, IL-6, and IL-8), adipokines (matrix metalloproteinase-1, PAI-1), and prostanoids (TBX2, PGE2) compared with SAT. Secretome proteomics revealed differences in immune/inflammatory response and extracellular matrix components. In vitro, VAT-conditioned media decreased hepatocyte and myotube insulin sensitivity, hepatocyte glucose handling, and increased basal activation of inflammatory signaling in myotubes compared with SAT. Depot-specific differences in adipose tissue secretome composition alter paracrine and endocrine signaling. The unique secretome of VAT has distinct and negative impact on hepatocyte and muscle insulin action.

One week of overeating upregulates angiogenic and lipolytic gene expression in human subcutaneous adipose tissue from exercise trained and untrained adults.

Effective storage of excess energy in abdominal subcutaneous adipose tissue during periods of overeating may help attenuate weight-gain-related insulin resistance. The objective of this study was to assess changes in the expression of factors regulating abdominal subcutaneous adipose tissue storage capacity in response to a brief exposure to overeating in nonobese adults. Because exercise can alter the expression of genes involved in regulating adipose tissue storage capacity, we compared the responses to overeating in regular exercisers (EX, n = 11) and nonexercisers (nonEX, n = 11). Abdominal subcutaneous adipose tissue samples and oral glucose tolerance tests were performed before and after participants ate 30% above their estimated daily energy requirements for 1 week. Both EX and nonEX gained ∼1 kg (P < 0.01), and Matsuda insulin sensitivity index was reduced ∼15% (P = 0.04) in both groups. Gene expression of factors involved in lipid metabolism (HSL, ATGL, DGAT, and PPARγ) and angiogenesis (HIF1α and KDR) were increased (P < 0.05), with no differences observed between EX and nonEX. In contrast, protein abundance of these factors did not change. The modest overeating stimulus did not increase markers of inflammation in the systemic circulation or adipose tissue. Overall, our findings indicate that a brief and modest overeating stimulus can impair insulin sensitivity and upregulate genes involved in abdominal adipose tissue storage capacity similarly in exercisers and nonexercisers. ClinicalTrials.gov ID#: NCT02701738.

Low-Dose Insulin as an Antiscarring Therapy in Breast Surgery: A Randomized Controlled Trial.

BACKGROUND: The role of insulin in expediting wound healing is firmly established within the context of major trauma and burns; however, only limited clinical evidence exists as to its effects on scar formation. This study aims to build on previous laboratory work to examine the potential antiscarring properties of insulin in a clinical environment. METHODS: Ninety-one patients undergoing bilateral aesthetic breast operations were recruited to receive low-dose insulin and placebo injections to the medial 3 cm of their submammary incisions within the context of a randomized, intrapatient, placebo-controlled trial, and scar quality was assessed at 3-, 6-, and 12-month reviews using the Manchester Scar Scale. RESULTS: Across the cohort at 12-month review, the insulin-treated scars had lower scar scores (p = 0.055) compared with placebo. Subgroup analysis of individuals with heavier scars showed that median scar scores were significantly lower for the insulin-treated scars with regard to both scar contour (p = 0.048) and scar distortion (p = 0.045). CONCLUSIONS: Subcutaneous insulin injections reduced the appearance of scarring in this study compared with placebo. The greatest effect was seen in those participants who showed heavier scars and, as such, insulin has a role as an antiscarring therapy in individuals likely to be affected by heavier scarring. Further research is required to more precisely delineate which subjects may benefit most from this treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Effect of oral supplementation of composite leaf extract of medicinal plants on biomarkers of oxidative stress in induced diabetic Wistar rats.

Present study was conducted to evaluate the effect of oral supplementation of composite extract of leaves (CLE) of four medicinal plants; Aegle marmelos, Ocimum sanctum, Murraya koenigii and Azadirachta indica on markers of oxidative stress in brain tissues of alloxan-induced diabetic rats in vivo. Enhanced lipid peroxidation, protein oxidation and reduced antioxidative defence systems were measured in brain tissues of diabetic rats. Supplementation of CLE, once in a day for 35 days significantly (p < .05) protected the peroxidation of lipid, oxidation of protein and ameliorated the antioxidant defence in brain tissue of diabetic rats. It was observed that the insulin-like effect of CLE was dose dependent; higher effect at higher doses. The results of the study suggest that supplementation CLE may provide an overall homeostasis and significant neuro-protection through rescuing brain cells from oxidative abuse and accelerating brain antioxidative defence during advanced stage of hyperglycaemia.

Transient neonatal diabetes mellitus and activating mutation in the KCNJ11 gene in two siblings.

Transient neonatal diabetes mellitus is a rare disease usually associated with chromosome 6 abnormalities. Mutations of the genes encoding the potassium channel are rarely associated with these transitional forms. Herein, we report the clinical features of two siblings with a heterozygous mutation C679 G>A in the KCNJ11 gene.

Comparative study between two recombinant human NPH insulin formulations for the treatment of type 2 diabetes mellitus.

OBJECTIVE: To compare the effects of the neutral protamine Hagedorn (NPH) recombinant human insulin formulations Gansulin and Humulin N® on the glycemic control of patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: Prospective, double-blind, randomized, parallel, single-center study of 37 individuals with T2DM treated with NPH insulin formulations. The Tukey-Kramer test for multiple comparisons, the Wilcoxon paired comparison test and the Chi-Square test were used for the statistical analyses. The significance level was set at 5% (p < 0.05). RESULTS: The NPH insulin formulations Humulin and Gansulin similarly reduced the HbA1c levels observed at the end of the study compared with the values obtained at the beginning of the study. In the Humulin group, the initial HbA1c value of 7.91% was reduced to 6.56% (p < 0.001), whereas in the Gansulin group, the reduction was from 8.18% to 6.65% (p < 0.001). At the end of the study, there was no significant difference between the levels of glycated hemoglobin (p = 0.2410), fasting plasma glucose (FG; p = 0.9257) and bedtime plasma glucose (BG; p = 0.3906) between the two insulin formulations. There was no nt difference in the number of hypoglycemic events between the two insulin formulations, and no severe hyp episodes were recorded. CONCLUSION: This study demonstrated similar glycemic control by NPH insulin Gansulin compared with human insulin Humulin N® in patients with T2DM.

The Relationship Between Serum Neuron-Specific Enolase Levels and Severity of Bleeding and Functional Outcomes in Patients With Nontraumatic Subarachnoid Hemorrhage.

BACKGROUND: The value of neuron-specific enolase (NSE) in predicting clinical outcomes has been investigated in a variety of neurological disorders. OBJECTIVE: To investigate the associations of serum NSE with severity of bleeding and functional outcomes in patients with subarachnoid hemorrhage (SAH). METHODS: We retrospectively reviewed the records of patients with SAH from June 2008 to June 2012. The severity of SAH bleeding at admission was measured radiographically with the Fisher scale and clinically with the Glasgow Coma Scale, Hunt and Hess grade, and World Federation of Neurologic Surgeons scale. Outcomes were assessed with the modified Rankin Scale at discharge. RESULTS: We identified 309 patients with nontraumatic SAH, and 71 had NSE testing. Median age was 54 years (range, 23-87 years), and 44% were male. In multivariable analysis, increased NSE was associated with a poorer Hunt and Hess grade (P = .003), World Federation of Neurologic Surgeons scale score (P < .001), and Glasgow Coma Scale score (P = .003) and worse outcomes (modified Rankin Scale at discharge; P = .001). There was no significant association between NSE level and Fisher grade (P = .81) in multivariable analysis. CONCLUSION: We found a significant association between higher NSE levels and poorer clinical presentations and worse outcomes. Although it is still early for any relevant clinical conclusions, our results suggest that NSE holds promise as a tool for screening patients at increased risk of poor outcomes after SAH.

Prolonged use of human insulin increases breast cancer risk in Taiwanese women with type 2 diabetes.

BACKGROUND: Human insulin is commonly used to treat hyperglycemia in patients with diabetes, but its potential link with female breast cancer is under debate. This study investigated whether human insulin use might be associated with breast cancer risk in Taiwanese women with type 2 diabetes. METHODS: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,033 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the adjusted hazard ratios were estimated by Cox regression. The potential risk modification by concomitant treatment with metformin, statin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) was also evaluated. RESULTS: There were 59,798 ever-users and 422,235 never-users of human insulin, with respective numbers of incident breast cancer of 559 (0.93 %) and 4,711 (1.12 %), and respective incidence of 207.9 and 215.1 per 100,000 person-years. The overall adjusted hazard ratio (95 % confidence interval) did not show a significant association with insulin [1.033 (0.936-1.139)]. However, patients in the third tertiles of dose-response parameters might show a significantly higher risk of breast cancer while compared to never-users: 1.185 (1.026-1.368), 1.260 (1.096-1.450) and 1.257 (1.094-1.446) for ≥67 months for time since starting insulin, ≥39,000 units for cumulative dose of insulin, and ≥21.8 months for cumulative duration of insulin, respectively. Additional analyses suggested that the breast cancer risk associated with human insulin use might be beneficially modified by concomitant use of metformin, statin and ACEI/ARB. CONCLUSIONS: This study discloses a significantly higher risk of breast cancer associated with prolonged use of human insulin. The increased risk of breast cancer associated with human insulin use may be modified by medications such as metformin, statin and ACEI/ARB.

Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension.

AIMS: To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs). METHODS: EDITION 2 (NCT01499095) was a randomized, 6-month, multicentre, open-label, two-arm, phase IIIa study investigating once-daily Gla-300 versus Gla-100, plus OADs (excluding sulphonylureas), with a 6-month safety extension. RESULTS: Similar numbers of participants in each group completed 12 months of treatment [Gla-300, 315 participants (78%); Gla-100, 314 participants (77%)]. The reduction in glycated haemoglobin was maintained for 12 months with both treatments: least squares (LS) mean (standard error) change from baseline -0.55 (0.06)% for Gla-300 and -0.50 (0.06)% for Gla-100; LS mean difference -0.06 [95% confidence interval (CI) -0.22 to 0.10)%]. A significant relative reduction of 37% in the annualized rate of nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia was observed with Gla-300 compared with Gla-100: rate ratio 0.63 [(95% CI 0.42-0.96); p = 0.031], and fewer participants experienced ≥1 event [relative risk 0.84 (95% CI 0.71-0.99)]. Severe hypoglycaemia was infrequent. Weight gain was significantly lower with Gla-300 than Gla-100 [LS mean difference -0.7 (95% CI -1.3 to -0.2) kg; p = 0.009]. Both treatments were well tolerated with a similar pattern of adverse events (incidence of 69 and 60% in the Gla-300 and Gla-100 groups). CONCLUSIONS: In people with type 2 diabetes treated with Gla-300 or Gla-100, and non-sulphonylurea OADs, glycaemic control was sustained over 12 months, with less nocturnal hypoglycaemia in the Gla-300 group.

Interactions of short-acting, intermediate-acting and pre-mixed human insulins with free radicals--Comparative EPR examination.

Electron paramagnetic resonance (EPR) spectroscopy was used to examine insulins interactions with free radicals. Human recombinant DNA insulins of three groups were studied: short-acting insulin (Insuman Rapid); intermediate-acting insulins (Humulin N, Insuman Basal), and pre-mixed insulins (Humulin M3, Gensulin M50, Gensulin M40, Gensulin M30). The aim of an X-band (9.3GHz) study was comparative analysis of antioxidative properties of the three groups of human insulins. DPPH was used as a stable free radical model. Amplitudes of EPR lines of DPPH as the paramagnetic free radical reference, and DPPH interacting with the individual tested insulins were compared. For all the examined insulins kinetics of their interactions with free radicals up to 60 min were obtained. The strongest interactions with free radicals were observed for the short-acting insulin - Insuman Rapid. The lowest interactions with free radicals were characteristic for intermediate-acting insulin - Insuman Basal. The pre-mixed insulins i.e. Humulin M3 and Gensulin M50 revealed the fastest interactions with free radicals. The short acting, intermediate acting and premixed insulins have been found to be effective agents in reducing free radical formation in vitro and should be further considered as potential useful tools in attenuation of oxidative stress in diabetic patients.

Improved limit of detection and quantitation development and validation procedure for quantification of zinc in Insulin by atomic absorption spectrometry.

A simple and expeditious analytical method for determination of zinc in human insulin isophane suspension by flame atomic absorption spectrophotometer (FAAS) was validated. The method was carried out on atomic absorption spectrometer with 0.4 nm bandwidth, 1.0 filter factor on deuterium (D2) background correction. The integration time was set at 3.0 second with 5.0 mA lamp current. The parameters of method validation showed adequate linearity, efficiency and relative standard deviation values were between 0.64%-1.69% (n=7), 1.31%-1.58% (n=10) for repeatability and intermediate precision respectively. The limit of detection 0.0032 µg/mL, 0.0173 µg/mL, 0.0231 µg/mL and limit of quantitation 0.0107µg/mL, 0.0578 µg/mL, 0.0694 µg/mL based on signal to noise (SN), calibration curve method (CCM) and fortification of blank (FB) were obtained respectively. The percentages of recovery for low, medium and high spiked concentration levels of zinc in human insulin were 99.38 ± 0.04 to 100.3 ± 0.03, 98.45 ± 0.38 to 100.3 ± 0.07 and 99.42 ± 0.03 to 99.42 ± 0.08 respectively. With the use of this method, five samples from each vial of human insulin isophane suspension were analyzed and the zinc content was determined. The zinc content were 22.1 ± 0.025 µg/mL and 24.3 ± 0.028 µg/mL which compliance the British Pharmacopoeia standard.

Association between hypoglycemia and the type of insulin in diabetic patients treated with multiple injections: an observational study.

INTRODUCTION: Hypoglycemia may have serious health consequences; therefore, it is important to expand knowledge on the factors that increase its prevalence. OBJECTIVES: The aim of the study was to evaluate the effect of the type of insulin-human vs. analogue-on the incidence of mild and severe hypoglycemia, body weight, and hemoglobin A1c (HbA1c) levels. PATIENTS AND METHODS: A total of 203 diabetic patients treated with intensive insulin therapy completed the questionnaire on hypoglycemia at baseline and at 3 and 6 months of the follow­up. Body weight and HbA1c levels were measured at baseline and at 6 months. Incidence of mild and severe hypoglycemia, body weight, and HbA1c levels were compared between patients treated with short­acting analogue and those treated with short­acting human insulin (regardless of the type of long­acting insulin used) and between patients receiving short- and long­acting analogue insulin and those receiving short- and long­acting human insulin. A multiple logistic regression analysis was used to find independent risk factors of severe hypoglycemia. RESULTS: At baseline, mild hypoglycemia was more common in patients receiving insulin analogue. There were no differences between the subgroups in the incidence of severe hypoglycemia, HbA1c levels, and body weight. Male sex, older age, and the dose of long­acting insulin were independently associated with a higher incidence of severe hypoglycemia. Type 2 diabetes and higher body weight were associated with a lower risk of severe hypoglycemia. CONCLUSIONS: Our results suggest that use of insulin analogues may predispose to more frequent episodes of mild hypoglycemia, but it does not increase the incidence of severe hypoglycemia in patients on intensive insulin therapy. Insulin analogues are not different from human insulin in terms of the effects on HbA1c levels and body mass.

Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows administered long-acting insulins. Western blot analysis of mammary tissue collected by biopsy indicated that the ratios of phosphorylated protein kinase b (Akt) to total Akt and phosphorylated ribosomal protein S6 (rpS6) to total rpS6 were not affected by long-acting insulins. Modestly elevating insulin activity in lactating dairy cows using long-acting insulins altered milk composition and metabolism. Future research should explore mechanisms by which either insulin concentrations or insulin signaling pathways in the mammary gland can be altered to enhance milk fat and protein production.

Cancer incidence among those initiating insulin therapy with glargine versus human NPH insulin.

OBJECTIVE: To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer. RESEARCH DESIGN AND METHODS: We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality. RESULTS: More patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer. The overall HR was 1.12 (95% CI 0.95-1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses. CONCLUSIONS: Patients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing.

A comparison of insulin detemir and neutral protamine Hagedorn (isophane) insulin in the treatment of diabetes: a systematic review.

The aim of this review is to summarize the clinical efficacy, tolerability and safety data of insulin detemir, and compare its use with that of neutral protamine Hagedorn (NPH) insulin in randomized controlled trials in people with type 1 or type 2 diabetes. A literature search was conducted with PubMed using predefined search terms. Studies were included if they met the following criteria: randomized, controlled trial, comparison of insulin detemir with NPH insulin, non-hospitalized adults aged ≥18 years with either type 1 or type 2 diabetes, and study duration of ≥12 weeks. The following types of studies were excluded: non-randomized controlled trials, studies of mixed cohorts of patients with type 1 or type 2 diabetes that did not report results separately, pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or health-economic analyses. Fourteen publications met the inclusion criteria. Nine studies in people with type 1 diabetes and three studies in people with type 2 diabetes, using insulin detemir in a basal-bolus regimen were included. Two studies were in people with type 2 diabetes using insulin detemir with oral antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes, insulin detemir treatment provided similar or better glycaemic control, lower within-subject variability, similar or lower frequency of hypoglycaemia and less weight gain when compared with NPH insulin.

Improved glycemic control and acute complications among children with type 1 diabetes mellitus in Moshi, Tanzania.

OBJECTIVE: There are an estimated 1000 children with diabetes in Tanzania. Recently, the first two pediatric endocrinologists, trained in the European Society for Paediatric Endocrinology (ESPE)/International Society for Paediatric and Adolescent Diabetes (ISPAD) program in Nairobi, Kenya, entered practice. The purpose of this study was to prospectively assess the impact of a 6-month diabetes management and education program on glycemic control and acute complications in children and adolescents in Tanzania. RESEARCH DESIGN AND METHODS: Eighty-one patients aged 3-19 yr were enrolled. All were on split-dose Insulatard (Neutral Protamine Hagedorn) and Actrapid (soluble, regular) insulin, and were given three glucose test strips per week. Children were seen in clinic an average of six times over 6 months and received 3 h of diabetes education. A structured questionnaire evaluated social demographic data and acute complications. RESULTS: Despite regular clinic attendance, diabetes education, and provision of insulin, hemoglobin A1c (HbA1c) levels did not improve. Four children (5%) had HbA1c 7.5%, 22 (28%) HbA1c 7.5-10%, 9 (24%) HbA1c 11-12.5%, and 36 (44%) HbA1c >12.5%. There was a substantial reduction in severe hypoglycemia, with 17% of subjects experiencing this acute complication compared to 52% in the 6 months prior to study enrolment. Six children were admitted in diabetic ketoacidosis during the study compared to three during the previous 6 months. Twenty-six children (36%) reported missing >6 doses of insulin (but only two lacked insulin). CONCLUSIONS: Diabetes education significantly reduced the risk of severe hypoglycemia, but better glycemic control of diabetes was not attained. Further study is needed to explore factors to improve glycemic control including increased testing, or perhaps different insulin regimens.

Permanent neonatal diabetes due to a novel insulin signal peptide mutation.

We report a rare case of permanent neonatal diabetes (PND) due to insulin (INS) gene mutation in a 51-month-old girl who presented with hyperglycemia in the neonatal period. Mutational analysis of KCNJ11 and INS was performed and this detected a novel heterozygous c.38T>G (p.Leu13Arg) INS de novo mutation. The non-conservative change substitutes the highly conserved L(13) residue within the hydrophobic core region of the preproinsulin signal peptide. Given the frequent tendency of heterozygous INS mutations to exhibit dominant negative disease pathogenesis, it is likely that the mutant preproinsulin perturbed the non-mutant counterpart progression and processing within the ß-cells, and this resulted to a permanent form of congenital diabetes.