Increased risk of death following recurrent ketoacidosis admissions: a Brazilian cohort study of young adults with type 1 diabetes.

BACKGROUND: Recurrent DKA (rDKA) remains an acute type 1 diabetes complication even in post-insulin era. This study aimed to analyze the predictors and effects of rDKA on the mortality of patients with type 1 diabetes. METHODS: Patients hospitalized (n = 231) wih diabetic ketoacidosis (between 2007 and 2018) were included. Laboratorial and clinical variables were collected. Mortality curves were compared in four groups: diabetic ketoacidosis as a new-onset type 1 diabetes (group A), single diabetic ketoacidosis episode after diagnosis of type 1 diabetes (group B), 2-5 diabetic ketoacidosis events (group C), and > 5 diabetic ketoacidosis events during follow-up period (group D). RESULTS: During the follow-up period (approximately 1823 days), the mortality rate was 16.02% (37/231). The median age at death was 38.7 years. In the survival curve analysis, at 1926 days (5 years), the probabilities of death were indicated by ratios of 7.78%, 4.58%, 24.40%, and 26.63% in groups A, B, C, and D, respectively. One diabetic ketoacidosis episode compared with ≥ 2 events had a relative risk of 4.49 (p = 0.004) of death and > 5 events had 5.81 (p = 0.04). Neuropathy (RR 10.04; p < 0.001), retinopathy (relative risk 7.94; p < 0.01), nephropathy (RR 7.10; p < 0.001), mood disorders (RR 3.57; p = 0.002), antidepressant use (RR 3.09; p = 0.004), and statin use (RR 2.81; p = 0.0024) increased the risk of death. CONCLUSIONS: Patients with type 1 diabetes with > 2 diabetic ketoacidosis episodes have four times greater risk of death in 5 years. Microangiopathies, mood disorders, and use of antidepressants and statins were important risk factors for short-term mortality.

Residual ß-cell function in Brazilian Type 1 diabetes after 3 years of diagnosis: prevalence and association with low presence of nephropathy.

BACKGROUND: Persistence of ß cell-function in Type 1 diabetes (T1D) is associated with glycaemia stability and lower prevalence of microvascular complications. We aimed to assess the prevalence of residual C- peptide secretion in long-term Brazilian childhood onset T1D receiving usual diabetes care and its association to clinical, metabolic variables and microvascular complications. METHODS: A cross-sectional observational study with 138 T1D adults with ≥ 3 years from the diagnosis by routine diabetes care. Clinical, metabolic variables and microvascular complications were compared between positive ultra-sensitive fasting serum C-peptide (FCP +) and negative (FCP-) participants. RESULTS: T1D studied had ≥ 3 yrs. of diagnosis and 60% had FCP > 1.15 pmol/L. FCP + T1D were older at diagnosis (10 vs 8 y.o; p = 0.03) and had less duration of diabetes (11 vs 15 y.o; p = 0.002). There was no association between the FCP + and other clinical and metabolic variable but there was inversely association with microalbuminuria (28.6% vs 13.4%, p = 0.03), regardless of HbA1c. FCP > 47 pmol/L were associated with nephropathy protection but were not related to others microvascular complications. CONCLUSION: Residual insulin secretion is present in 60% of T1D with ≥ 3 years of diagnosis in routine diabetes care. FCP + was positively associated with age of diagnosis and negatively with duration of disease and microalbuminuria, regardless of HbA1c.

Allogenic Adipose Tissue-Derived Stromal/Stem Cells and Vitamin D Supplementation in Patients With Recent-Onset Type 1 Diabetes Mellitus: A 3-Month Follow-Up Pilot Study.

Objective: To evaluate the short term safety and potential therapeutic effect of allogenic adipose tissue-derived stromal/stem cells (ASCs) + cholecalciferol in patients with recent-onset T1D. Methods: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 106 cells/kg) and cholecalciferol 2000 UI/day for 3 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide (CP), insulin dose, HbA1c, time in range (TIR), glucose variability (continuous glucose monitoring) and frequency of CD4+FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3). Results: 13 patients were included (8: group 1; 5: group 2). Their mean age and disease duration were 26.7 ± 6.1 years and 2.9 ± 1.05 months. Adverse events were transient headache (n = 8), mild local reactions (n = 7), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), mild floaters (n = 2), central retinal vein occlusion (n = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; p = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; p = 0.03) than group 2. In group 1, 2 patients became insulin free (for 4 and 8 weeks) and all were in honeymoon at T3 (vs. none in group 2; p = 0.01). CP variations did not differ between groups (-4.6 ± 29.1% vs. +2.3 ± 59.65%; p = 0.83). Conclusions: Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D. ClinicalTrials.gov registration: NCT03920397.

Hope matters to the glycemic control of adolescents and young adults with type 1 diabetes.

This study investigated the association of hope and its factors with depression and glycemic control in adolescents and young adults with type 1 diabetes. A total of 113 patients were invited to participate. Significant negative correlations were found between hope and HbA1c and also between hope and depression. Hope showed a significant association with HbA1c and depression in the stepwise regression model. Among the hope factors, "inner positive expectancy" was significantly associated with HbA1c and depression. This study supports that hope matters to glycemic control and depression. Intervention strategies focusing on hope should be further explored.

HDL cholesterol levels and weight are the main determinants of subclinical atherosclerosis in the young with type 1 diabetes and suitable glycaemic control.

The aim of this study was to evaluate subclinical atherosclerosis and related factors in young type 1 diabetes (T1D) patients and healthy peers. Carotid intima-media thickness (cIMT) and anthropometric/laboratorial data were obtained for 83 T1D patients (mean age 19.5 ± 4.0 years, disease duration 9.8 ± 4.8 years) and for 36 matched healthy subjects. Considering all the participants as one group, male sex (p = 0.008), weight (p = 0.016) and T1D (p < 0.001) were positively associated with a higher cIMT. High-density lipoprotein (HDL) (p = 0.036) was negatively associated with cIMT in T1D. In the male T1D patients, HDL ≤47.5 mg/dL had a sensitivity of 87.5% and specificity of 57% (p = 0.035) in detecting those belonging to a higher cIMT tercile. In conclusion, weight and T1D were associated with increased cIMT. HDL levels ≤47.5 mg/dL were related to a higher cIMT in male T1D patients.

The impact of knowledge about diabetes, resilience and depression on glycemic control: a cross-sectional study among adolescents and young adults with type 1 diabetes.

BACKGROUND: The purpose of this study is to evaluate the relationship between glycemic control and the factors of knowledge about diabetes, resilience, depression and anxiety among Brazilian adolescents and young adults with type 1 diabetes. METHODS: This cross-sectional study included 85 adolescents and young adults with type 1 diabetes, aged between 11-22 years, with an average age of 17.7 ± 3.72 years. Glycemic control degree was evaluated through HbA1c. To assess psychosocial factors, the following questionnaires were used: resilience (Resilience Scale, RS) and anxiety and depression (Hospital Anxiety and Depression Scale, HADS). The Diabetes Knowledge Assessment Scale (DKNA) was used to assess knowledge about diabetes. RESULTS: Significant correlations were found between HbA1c and resilience, anxiety and depression. Multiple linear regression analysis revealed that the only variable which presented significant association with the value of HbA1c was depression. CONCLUSIONS: Depression has a significant association with higher HbA1c levels, as demonstrated in a regression analysis. The results suggest that depression, anxiety and resilience should be considered in the design of a multidisciplinary approach to type 1 diabetes, as these factors were significantly correlated with glycemic control. Glycemic control was not correlated with knowledge of diabetes, suggesting that theoretical or practical understanding of this disease is not by itself significantly associated with appropriate glycemic control (HbA1c = 7.5%).

Effect of cholecalciferol as adjunctive therapy with insulin on protective immunologic profile and decline of residual ß-cell function in new-onset type 1 diabetes mellitus.

OBJECTIVE: To evaluate the effect of vitamin D3 on cytokine levels, regulatory T cells, and residual ß-cell function decline when cholecalciferol (vitamin D3 administered therapeutically) is given as adjunctive therapy with insulin in new-onset type 1 diabetes mellitus (T1DM). DESIGN AND SETTING: An 18-month (March 10, 2006, to October 28, 2010) randomized, double-blind, placebo-controlled trial was conducted at the Diabetes Center of São Paulo Federal University, São Paulo, Brazil. PARTICIPANTS: Thirty-eight patients with new-onset T1DM with fasting serum C-peptide levels greater than or equal to 0.6 ng/mL were randomly assigned to receive daily oral therapy of cholecalciferol, 2000 IU, or placebo. MAIN OUTCOME MEASURE: Levels of proinflammatory and anti-inflammatory cytokines, chemokines, regulatory T cells, hemoglobin A1c, and C-peptide; body mass index; and insulin daily dose. RESULTS: Mean (SD) chemokine ligand 2 (monocyte chemoattractant protein 1) levels were significantly higher (184.6 [101.1] vs 121.4 [55.8] pg/mL) at 12 months, as well as the increase in regulatory T-cell percentage (4.55% [1.5%] vs 3.34% [1.8%]) with cholecalciferol vs placebo. The cumulative incidence of progression to undetectable (≤0.1 ng/mL) fasting C-peptide reached 18.7% in the cholecalciferol group and 62.5% in the placebo group; stimulated C-peptide reached 6.2% in the cholecalciferol group and 37.5% in the placebo group at 18 months. Body mass index, hemoglobin A1c level, and insulin requirements were similar between the 2 groups. CONCLUSIONS: Cholecalciferol used as adjunctive therapy with insulin is safe and associated with a protective immunologic effect and slow decline of residual ß-cell function in patients with new-onset T1DM. Cholecalciferol may be an interesting adjuvant in T1DM prevention trials.

A 12-wk follow-up study to evaluate the effects of mixing insulin lispro and insulin glargine in young individuals with type 1 diabetes.

OBJECTIVE: This study was performed to compare in real-life conditions the serum profile of insulin lispro (IL) after a subcutaneous (SC) injection, separate and mixed with insulin glargine (IG), using a sensitive radioimmunoassay for the specific determination of serum IL, and to evaluate the 12-wk effect of the mixture on glycemic control in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: The IL serum profiles were evaluated in 10 individuals with type 1 diabetes [age 21.9 ± 3.8 yr; diabetes duration 13.4 ± 4.9 yr; body mass index 25.1 ± 3.2 kg/m2; hemoglobin A1c (HbA1c) 8.3 ± 0.8%] during a mixed meal test (MMT) using IL and IG as separate (baseline) and mixed injection. The glycemic variability by continuous glucose monitoring system (CGMS) and the long-term diabetes control with HbA1c were also evaluated at baseline and after 12 wk mixing the two insulins. RESULTS: The mixture of IL with IG decreased IL maximum serum concentration (Cmax(IL) ) (29.4 ± 5.1 µU/mL vs. 13.7 ± 4.2 µU/mL; p = 0.03) without changing the time to reach the Cmax (Tmax(IL) ), the IL area under the curve (AUC(IL) (0-240) ), and the glucose dynamics during the MMT. The glucose variability and the HbA1c were equivalent to baseline after 12 wk mixing both insulins. CONCLUSIONS: These data suggest that mixing IL with IG immediately before the SC injection decreases IL serum peak concentration without affecting the glycemic profile after 12 wk in this group with type 1 diabetes mellitus.

Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p. T10I mutation / Lipoatrofia generalizada atípica e resistência insulínica grave devido à mutação p. T10I em heterozigose no gene LMNA

Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confirmed by DEXA (total body fat 8.6 percent). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identified a heterozygous substitution in exon 1 (c.29C>T) predicting a p.T10I mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.T10I mutation in LMNA gene.

As lipodistrofias são um grupo heterogêneo de doenças caracterizadas por perda de tecido adiposo e complicações metabólicas. As formas hereditárias mais importantes de lipodistrofias são: lipodistrofia congênita generalizada e lipodistrofia parcial familiar (LDPF). LDPF resulta de mutações no gene LMNA que codificam as lâminas tipo A. Além da LDPF, mutações no gene LMNA são responsáveis por outras doenças hereditárias, denominadas laminopatias. Descrevemos o caso de uma paciente de 15 anos de idade encaminhada por diabetes melito e hipertrigliceridemia grave. Ao exame físico, apresentava perda generalizada de gordura subcutânea que foi confirmada por DEXA (gordura corporal total 8,6 por cento). Como a paciente apresentava perda de gordura de início na puberdade e resistência insulínica, foi realizada análise molecular do gene LMNA. Identificamos uma substituição em heterozigose no éxon 1 (c.29C>T), resultando na mutação p.T10I. Em sumário, um caso de fenótipo atípico de lipodistrofia generalizada devido à mutação de novo p.T10I no gene LMNA é descrito.

Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p.T10I mutation.

Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confirmed by DEXA (total body fat 8.6%). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identified a heterozygous substitution in exon 1 (c.29C>T) predicting a p.T10I mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.T10I mutation in LMNA gene.

[Comparison between continuous subcutaneous insulin infusion and multiple daily injection regimens in adolescent with type 1 diabetes from a public health care system approach to severe hypoglycemia]. / Comparação entre a bomba de infusão de insulina subcutânea e o esquema de múltiplas doses de insulina em adolescentes com diabetes melito do tipo 1 da rede pública de saúde na abordagem da hipoglicemia grave.

OBJECTIVE: We compared the incidence of severe hypoglycemia episodes with therapy with multiple doses of insulin (MDI) and after changing to pump (CSII). PATIENTS AND METHODS: 7 T1DM patients with 14 years median and median duration of diabetes of 8 years. We analyzed insulin requirement (U/kg/day), BMI (Kg/m(2)), HbA1c (normal range: 3.5-6.7%) one year before and one year after changing therapy. The severe hypoglycemia episodes decreased from 1.3 to 0 episodes/patient/year; p = 0.00). The insulin requirement decreased from 1.33 +/- 0.26 U/Kg/day to 0.87 +/- 0.17 U/kg/day; p = 0.04 and HbA1c decreased from 8.7 +/- 0.7% to 7.8 +/- 0.9%; p = 0.05. CONCLUSION: CSII is efficient in decreasing severe hypoglycemia in a subgroup of T1DM using MDI also in Public Health Care System (PHCS) conditions. However, these finding should be reproduced by other Diabetes Care centers and cost studies are necessary to confirm the viability and possibility of this therapy, when necessary, to T1DM patients, which correspond to the majority of these individuals in our country, seeing in the PHCS.

Comparação entre a bomba de infusão de insulina subcutânea e o esquema de múltiplas doses de insulina em adolescentes com diabetes melito do tipo 1 da rede pública de saúde na abordagem da hipoglicemia grave / Comparison between continuous subcutaneous insulin infusion and multiple daily injection regimens in adolescent with type 1 diabetes from a public health care system approach to severe hypoglycemia

OBJETIVO: Avaliação comparativa da freqüência de hipoglicemia severa após mudança da terapia com múltiplas doses de insulina (MDI) para bomba de insulina subcutânea (BIISC). PACIENTES E MÉTODOS: Sete pacientes DM1, idade Mi = 14 anos e tempo médio de diabetes de 8 anos, comparados de acordo com a incidência de hipoglicemia, a dose total de insulina (U/Kg/d), IMC (Kg/m²) e HbA1c (vn: 3,5-6,7 por cento) 1 ano antes e 1 ano após a transferência de terapêutica. Houve redução significativa dos episódios de hipoglicemia severa (1,3 episódio/paciente/ano para zero episódio/paciente/ano; p = 0,04), na dose total diária de insulina (1,33 ± 0,26 U/Kg/dia para 0,87 ± 0,17 U/kg/dia; p = 0,04) e na HbA1c (8,7 ± 0,7 por cento para 7,8 ± 0,9 por cento; p = 0,05 com BIISC). Concluímos que a BIISC é eficaz e segura na redução de hipoglicemia severa em um subgrupo de pacientes DM1 com MDI. Entretanto, os resultados obtidos precisam ser reproduzidos em centros semelhantes e estudos de custo são necessários para que a sua viabilidade seja confirmada e aplicada nos sistemas públicos de saúde, que correspondem à maioria no nosso país.

OBJECTIVE: We compared the incidence of severe hypoglycemia episodes with therapy with multiple doses of insulin (MDI) and after changing to pump (CSII). PATIENTS AND METHODS: 7 T1DM patients with 14 years median and median duration of diabetes of 8 years. We analyzed insulin requirement (U/kg/day), BMI (Kg/m²), HbA1c (normal range: 3.5-6.7 percent) one year before and one year after changing therapy. The severe hypoglycemia episodes decreased from 1.3 to 0 episodes/patient/year; p = 0.00). The insulin requirement decreased from 1.33 ± 0.26 U/Kg/day to 0.87 ± 0.17 U/kg/day; p = 0.04 and HbA1c decreased from 8.7 ± 0.7 percent to 7.8 ± 0.9 percent; p = 0.05. CONCLUSION: CSII is efficient in decreasing severe hypoglycemia in a subgroup of T1DM using MDI also in Public Health Care System (PHCS) conditions. However, these finding should be reproduced by other Diabetes Care centers and cost studies are necessary to confirm the viability and possibility of this therapy, when necessary, to T1DM patients, which correspond to the majority of these individuals in our country, seeing in the PHCS.

Comparação entre as insulinas regular pré-jantar e NPH no almoço como a terceira aplicação de insulina no tratamento de adolescentes com diabetes melito do tipo 1 em um Serviço Público de Saúde / Comparison of pre-dinner regular versus pre-lunch NPH as a third insulin application in adolescents with type 1 diabetes from a Public Health Service

A maioria dos pacientes com diabetes do tipo 1 (DM1) são acompanhados em serviços de Saúde Pública. O controle glicêmico nas crianças, por várias razões, não atinge as metas desejadas. Neste estudo, comparamos 2 estratégias de otimização da administração de insulina em 53 adolescentes DM1 com controle glicêmico inadequado no esquema convencional (insulina NPH 2 vezes ao dia). Regime A: NPH + Regular (R) antes do café, insulina R antes do jantar e NPH ao deitar. Regime B: NPH + R antes do café e almoço e NPH ao deitar. O estudo clínico de coorte, longitudinal, aberto, randomizado com 12 meses de duração foi realizado em um hospital público. O IMC (A: 23,4±3,5Kg/m² x B: 23,5±0,8Kg/m²), a dose diária média de insulina (A: 1,04±0,28U/Kg/d x B: 1,08±0,22U/ Kg/d), assim como a freqüência de hipoglicemia severa (A: 9,4 por cento x B: 7,5 por cento), foi semelhante nos 2 grupos durante o estudo. Entretanto, a HbA1c ao final do estudo foi significativamente menor no regime B (9 por cento) comparado ao regime A (7,5 por cento; p= 0,05). Em conclusão, mostramos que a introdução da insulina NPH + R no almoço associada ao tradicional esquema de insulina NPH + R como desjejum pela manhã e NPH ao deitar é superior ao esquema de insulina R pré-jantar associada à insulina NPH + R pela manhã e NPH ao deitar para o controle glicêmico, não havendo diferenças com relação à variação de peso e freqüência de hipoglicemia entre os 2 esquemas. Deste modo, a utilização de 3 doses de insulina NPH por dia pode ser considerada uma opção eficaz e factível de ser utilizada em pacientes com DM1 assistidos em um Serviço Público de Saúde.

Early subclinical limited axial and large joint flexibility in type 1 diabetes mellitus adolescents.

OBJECTIVE: The objective of this study was to compare the axial and large joint mobility in adolescents with and without type 1 diabetes mellitus (DM1). PATIENT AND METHODS: To check this relationship, 72 DM1 adolescents aged 9-20 years were admitted into the trial and compared with 46 healthy control subjects aged 10-18 years. The youths were compared with regard to anthropometrics (age, proportion female/male, weight, height, and BMI) data. The years from DM1 diagnosis and HbA(1c) (index) were 4.9 +/- 3.6 years and 1.40 +/- 0.39%, respectively. The values of the tests of flexibility of the movements of cervical joint, the abduction of scapular, wrist and back-lumbar joints and abduction of lame-femoral were obtained through the Fleximeter. RESULTS: The DM1 patients and controls did not differ regarding age (DM1 median 16, range 9-20 years vs. controls 16, range 10-18 years) and BMI (DM1 mean+/-S.D. 21.49 +/- 3.69 kg/m(2) vs. controls 20.76 +/- 2.81 kg/m(2)). The scapular, back-lumbar, and lame-femoral flexibility were, respectively, significantly lower (P < .001) in DM1 adolescents (175 +/- 8 degrees , 107 +/- 4 degrees , 66 +/- 10 degrees) compared with controls (189 +/- 13, 116 +/- 14, 76 +/- 12), but the cervical joint mobility was the same in both groups (DM1: 98 +/- l2 degrees vs. control: 101 +/- 13 degrees). CONCLUSION: Thus, the results of our study show a subclinical limited axial and large joint mobility in DM1 adolescents. Future prospective studies are needed to ascertain whether the joint limitations found in these DM1 adolescents will persist into adulthood and play a role in the development of other diabetic complications.

[Comparison of pre-dinner regular versus pre-lunch NPH of a third insulin application in adolescents with type 1 diabetes from a Public Health Service]. / Comparação entre as insulinas regular pré-jantar e NPH no almoço como a terceira aplicação de insulina no tratamento de adolescentes com diabetes melito do tipo 1 em um Serviço Público de Saúde.

The majority of the type 1 Diabetes (DM1) patients are seen in Public Health Services. The management of these children, by several reasons, did not meet most of the standards for good diabetes control. In the present study we compare 2 different insulin treatment strategies in 53 uncontrolled DM1 adolescents despite a twice-a-day insulin regimen. A regimen: NPH + R before breakfast, R insulin before dinner and bedtime NPH. B regimen: NPH + R before breakfast and lunch and bedtime NPH. This was a 12-month open-label, randomized, clinical trial conducted in a Public Hospital. BMI (A: 23.4+/-3.5 Kg/m2 x B: 23.5+/-0.8 Kg/m2), average daily insulin dose (A: 1.04+/-0.28 U/Kg/d x B: 1.08+/-0.22 U/Kg/d) as well as the overall frequency of severe hypoglycemia (A: 9.4% x B: 7.5%) were similar in both groups during the study. However, HbA1c values at the end of the study were significantly lower in the B (9%) as compared to the A regimen (7,5%; p = 0.05). In conclusion, we have shown that breakfast and lunchtime NPH + R insulin plus bedtime NPH insulin is superior to pre-dinner R insulin plus breakfast and bedtime NPH insulin for overall glycemic control with similar weight status and comparable frequency of hypoglycemia. Thus, three times a day NPH insulin application is a feasible option for public service patients.