Dysglycemias in patients admitted to ICUs with severe acute respiratory syndrome due to COVID-19 versus other causes - a cohort study.

BACKGROUND: Dysglycemias have been associated with worse prognosis in critically ill patients with COVID-19, but data on the association of dysglycemia with COVID-19 in comparison with other forms of severe acute respiratory syndrome are lacking. This study aimed to compare the occurrence of different glycemic abnormalities in patients with severe acute respiratory syndrome and COVID-19 admitted to intensive care units versus glycemic abnormalities in patients with severe acute respiratory syndrome from other causes, to evaluate the adjusted attributable risk associated with COVID-19 and dysglycemia and to assess the influence of these dysglycemias on mortality. METHODS: We conducted a retrospective cohort of consecutive patients with severe acute respiratory syndrome and suspected COVID-19 hospitalized in intensive care units between March 11 and September 13, 2020, across eight hospitals in Curitiba-Brazil. The primary outcome was the influence of COVID-19 on the variation of the following parameters of dysglycemia: highest glucose level at admission, mean and highest glucose levels during ICU stay, mean glucose variability, percentage of days with hyperglycemia, and hypoglycemia during ICU stay. The secondary outcome was the influence of COVID-19 and each of the six parameters of dysglycemia on hospital mortality within 30 days from ICU admission. RESULTS: The sample consisted of 841 patients, of whom 703 with and 138 without COVID-19. Comparing patients with and without COVID-19, those with COVID-19 had significantly higher glucose peaks at admission (165 mg/dL vs. 146 mg/dL; p = 0.002) and during ICU stay (242 mg/dL vs. 187md/dL; p < 0.001); higher mean daily glucose (149.7 mg/dL vs. 132.6 mg/dL; p < 0.001); higher percentage of days with hyperglycemia during ICU stay (42.9% vs. 11.1%; p < 0.001); and greater mean glucose variability (28.1 mg/dL vs. 25.0 mg/dL; p = 0.013). However, these associations were no longer statistically significant after adjustment for Acute Physiology and Chronic Health Evaluation II scores, Sequential Organ Failure Assessment scores, and C-reactive protein level, corticosteroid use and nosocomial infection. Dysglycemia and COVID-19 were each independent risk factors for mortality. The occurrence of hypoglycemia (< 70 mg/dL) during ICU stay was not associated with COVID-19. CONCLUSION: Patients with severe acute respiratory syndrome due to COVID-19 had higher mortality and more frequent dysglycemia than patients with severe acute respiratory syndrome due to other causes. However, this association did not seem to be directly related to the SARS-CoV-2 infection.

Portuguese-Brazilian evidence-based guideline on the management of hyperglycemia in type 2 diabetes mellitus.

BACKGROUND: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. METHODS: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction (< 40%) and glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.

IL18 Gene Polymorphism Influences Age of Onset of DM1 in African Ancestry Brazilians.

The aim of this study was to investigate the relationship of two single nucleotide polymorphisms (SNPs) in the interleukin-18 ( IL18 ) gene (rs187238, g.-137G > C; rs1946518, g.-607C > A) and one SNP of the IL12B gene (rs3212227 g.*159A > C, 3'UTR) with the age of onset for type 1 diabetes mellitus (DM1). A total of 1,101 patients with DM1 enrolled in 13 centers from different regions of Brazil were genotyped with TaqMan assay and classified according to the ancestry. Our results show that an SNP in IL18 gene could be associated with DM1 age onset, taking into account that this studied variation affects gene expression.

Postpartum Reclassification of Glycemic Status in Women with Gestational Diabetes Mellitus and Associated Risk Factors.

UNLABELLED: Objective The aims of the study were to evaluate, after pregnancy, the glycemic status of women with history of gestational diabetes mellitus (GDM) and to identify clinical variables associated with the development of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). Methods Retrospective cohort of 279 women with GDM who were reevaluated with an oral glucose tolerance test (OGTT) after pregnancy. Characteristics of the index pregnancy were analyzed as risk factors for the future development of prediabetes (IFG or IGT), and T2DM. RESULTS: T2DM was diagnosed in 34 (12.2%) patients, IFG in 58 (20.8%), and IGT in 35 (12.5%). Women with postpartum T2DM showed more frequently a family history of T2DM, higher pre-pregnancy body mass index (BMI), lower gestational age, higher fasting and 2-hour plasma glucose levels on the OGTT at the diagnosis of GDM, higher levels of hemoglobin A1c, and a more frequent insulin requirement during pregnancy. Paternal history of T2DM (odds ratio [OR] = 5.67; 95% confidence interval [95%CI] = 1.64-19.59; p = 0.006), first trimester fasting glucose value (OR = 1.07; 95%CI = 1.03-1.11; p = 0.001), and insulin treatment during pregnancy (OR = 15.92; 95%CI = 5.54-45.71; p < 0.001) were significant independent risk factors for the development of T2DM. Conclusion A high rate of abnormal glucose tolerance was found in women with previous GDM. Family history of T2DM, higher pre-pregnancy BMI, early onset of GDM, higher glucose levels, and insulin requirement during pregnancy were important risk factors for the early identification of women at high risk of developing T2DM. These findings may be useful for developing preventive strategies.

The rs10885122 polymorphism of the adrenoceptor alpha 2A (ADRA2A) gene in Euro-Brazilians with type 2 diabetes mellitus.

OBJECTIVE: To investigate the association of the rs10885122G>T polymorphism in the ADRA2A gene in a Euro-Brazilian sample of healthy (controls) and type 2 diabetic (T2D) subjects. SUBJECTS AND METHODS: We used fluorescent probes (TaqMan) to genotype 241 subjects, that is, 121 healthy and 120 T2D subjects, who were classified based on the Brazilian Diabetes Association (2013) and American Diabetes Association (2014) criteria. RESULTS: The genotype and allele frequencies showed no significant (P > 0.05) difference between the two studied groups. The minor allele (T) frequencies (95%CI) for rs10885122 were 19% (14-24%) and 20% (15-26%) for healthy and T2D groups, respectively. Carriers of the T allele (genotypes GT+TT) were significantly associated (P = 0.016) with approximately a 7-kg body weight reduction compared with the genotype GG, which was only found in the T2D group. CONCLUSION: The rs10885122G>T polymorphism of the ADRA2A gene was not associated with T2D in Euro-Brazilians, and carriers of the T allele had lower body weight in the presence of T2D.

Polymorphisms in FTO and TCF7L2 genes of Euro-Brazilian women with gestational diabetes.

OBJECTIVE: To investigate the association between fat mass and obesity-associated (FTO) gene polymorphisms rs8050136C>A and rs9939609T>A, and transcription factor 7-like 2 (TCF7L2) gene polymorphisms rs12255372G>T and rs7903146C>T, in a sample group of pregnant Euro-Brazilian women with or without gestational diabetes mellitus (GDM). METHODS: Subjects were classified as either healthy pregnant control (n=200) or GDM (n=200) according to the 2010 criteria of the American Diabetes Association. The polymorphisms were genotyped using fluorescent probes (TaqMan®). RESULTS: All groups were in the Hardy-Weinberg equilibrium. The genotype and allele frequencies of the examined polymorphisms did not exhibit significant difference (P>0.05) between the groups. In the healthy and GDM pregnant women groups, the A-allele frequencies (95% CI) of FTO polymorphisms rs8050136 and rs9939609 were 39% (34-44%); 38% (33-43%) and 40% (35-45%); 41% (36-46%), respectively; and the T-allele frequencies of TCF7L2 polymorphisms rs12255372 and rs7903146 were 30% (26-35%), 32% (27-37%) and 29% (25-34%), 36% (31-41%), respectively. CONCLUSION: The examined polymorphisms were not associated with GDM in the Euro-Brazilian population studied.

Health-related quality of life in patients with type 1 diabetes mellitus in the different geographical regions of Brazil: data from the Brazilian Type 1 Diabetes Study Group.

BACKGROUND: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities. METHODS: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected. RESULTS: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North-Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined. CONCLUSIONS: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Reproducibility of methods used for the assessment of autonomous nervous system's function.

OBJECTIVE: The objective of this study is to investigate the influence of the day-to-day variability of the measures of heart rate variability (HRV) on the sample size calculation for the study of cardiac autonomic neuropathy. MATERIAL AND METHODS: We analyzed HRV in the frequency domain [very low (VLF), low (LF), and high frequency (HF) bands] and in the time domain [the root mean squared of successive RR intervals differences (RMSSD); the mean RR intervals (RRNN); the standard deviation of RR intervals (SDNN) and the coefficient of variation (CV)] during a 5-min electrocardiogram record. We also analyzed the heart rate response to deep breathing [expiration:inspiration ratio], to the Valsalva maneuver and to standing [maximum:minimum ratio] and the blood pressure response to standing. The day-to-day variability was assessed by calculating the within-subject standard deviations (WSSD), limits of agreement, typical errors and the ratio of the WSSD to the mean values obtained on days 1 and 2 (WSSD/GM). RESULTS: Sixty-seven healthy subjects (45 females), aged 27 (19-39) years, were recruited. The RMSSD, CV, VLF, LF, HF and blood pressure response to standing showed marked variability (WSDD/GM (%)=237.7, 455.1, 69.9, 126.5, 81.3 and 380.5, respectively), while the RRNN, SDNN, Valsalva, expiration:inspiration and maximum:minimum ratio showed less variability (WSSD/GM (%)=6.4, 24.5, 18.6, 11.0 and 14.1, respectively). The minimum differences expected to be statistically significant for the autonomic measurements were calculated. CONCLUSION: Some tests that assess HRV showed adequate reproducibility. This study allows the determination of a sample size calculation for longitudinal or drug-testing studies.

Prevalence of adults with type 1 diabetes who meet the goals of care in daily clinical practice: a nationwide multicenter study in Brazil.

OBJECTIVE: To determine the prevalence of patients with type 1 diabetes mellitus who meet the glycemic and cardiovascular (CV) risk factors goals and the frequency of screening for diabetic complications in Brazil according to the American Diabetes Association guidelines. RESEARCH DESIGN AND METHODS: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 1774 adult patients (56.8% females, 57.2% Caucasians) aged 30.3 ± 9.8 years with diabetes duration of 14.3 ± 8.8 years. RESULTS: Systolic blood pressure was at goal in 40.3% and diastolic blood pressure was at goal in 26.6% of hypertensive patients. LDL cholesterol and HbA1c were at the goal in 45.2% and 13.2% of the patients, respectively. Overweight was presented in 25.6% and obesity in 6.9%. Among those with more than 5 years of disease, screening for retinopathy was performed in the preceding year in 70.1%. Nephropathy and feet complications were screened in 63.1% and 65.1%, respectively. CONCLUSIONS: The majority of patients did not meet metabolic control goals and a substantial proportion was not screened for diabetic complications. These issues may increase the risk of chronic complications and negatively impact public health.

Postpartum Reclassification of Glycemic Status in Women with Gestational Diabetes Mellitus and Associated Risk Factors / Reclassificação pós-parto do estado glicêmico em mulheres com diabetes mellitus gestacional e fatores de risco associados

Abstract Objective The aims of the study were to evaluate, after pregnancy, the glycemic status of women with history of gestational diabetes mellitus (GDM) and to identify clinical variables associated with the development of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). Methods Retrospective cohort of 279 women with GDM who were reevaluated with an oral glucose tolerance test (OGTT) after pregnancy. Characteristics of the index pregnancy were analyzed as risk factors for the future development of prediabetes (IFG or IGT), and T2DM. Results: T2DM was diagnosed in 34 (12.2%) patients, IFG in 58 (20.8%), and IGT in 35 (12.5%). Women with postpartum T2DM showed more frequently a family history of T2DM, higher pre-pregnancy body mass index (BMI), lower gestational age, higher fasting and 2-hour plasma glucose levels on the OGTT at the diagnosis of GDM, higher levels of hemoglobin A1c, and a more frequent insulin requirement during pregnancy. Paternal history of T2DM (odds ratio [OR] =5.67; 95% confidence interval [95%CI] =1.64-19.59; p =0.006), first trimester fasting glucose value (OR =1.07; 95%CI =1.03-1.11; p =0.001), and insulin treatment during pregnancy (OR =15.92; 95%CI =5.54-45.71; p < 0.001) were significant independent risk factors for the development of T2DM. Conclusion A high rate of abnormal glucose tolerance was found in women with previous GDM. Family history of T2DM, higher pre-pregnancy BMI, early onset of GDM, higher glucose levels, and insulin requirement during pregnancy were important risk factors for the early identification of women at high risk of developing T2DM. These findings may be useful for developing preventive strategies.

Objetivo Os objetivos do estudo foram avaliar o estado glicêmico de mulheres com história de diabetes mellitus gestacional (DMG) após o parto e identificar fatores associados ao desenvolvimento de diabetes mellitus tipo 2 (DM2), glicemia de jejum alterada (GJA) e tolerância diminuída à glicose (TDG). Métodos Coorte retrospectiva de 279 mulheres com DMG reavaliadas com um teste oral de tolerância à glicose (TOTG) após a gestação. Foram analisados fatores prognósticos da gestação índice e fatores de risco para o futuro desenvolvimento de pré-diabetes (GJA ou TDG) e DM2. Resultados: Diagnosticou-se DM2 em 34 pacientes (12,2%), GJA em 58 (20,8%) e TDG em 35 (12,5%). Mulheres que evoluíram para DM2 apresentaram maior frequência de história familiar de DM2, índice de massa corporal (IMC) pré-gestacional mais elevado, menor idade gestacional, níveis superiores de glicemia de jejum e 2 horas após glicose no TOTG ao diagnóstico do DMG, hemoglobina glicada mais elevada, e uso mais frequente de insulina na gestação. História paterna de DM2 (odds ratio [OR] = 5,67; intervalo de confiança de 95% [IC95%] = 1,64-19,59; p = 0,006), glicemia de jejum do primeiro trimestre (OR = 1,07; IC95% = 1,03-1,11; p = 0,001) e o uso de insulina na gestação (OR = 15,92; IC95% = 5,54-45,71; p < 0,001) foram fatores de risco independentes para o desenvolvimento de DM2. Conclusão Houve elevada incidência de alterações no metabolismo da glicose em mulheres com DMG prévio. História familiar de DM2, IMC pré-gestacional elevado, DMG diagnosticado mais precocemente na gestação, com glicemias mais elevadas e necessidade de insulina, foram importantes fatores de risco associados à identificação precoce de mulheres com alto risco de desenvolvimento de DM2. Este conhecimento pode ser útil para o desenvolvimento de estratégias de prevenção.

[Markers of diagnosis and treatment in 924 pregnancies with gestational diabetes mellitus]. / Marcadores para o diagnóstico e tratamento de 924 gestações com diabetes melito gestacional.

OBJECTIVES: To evaluate the epidemiological profile and outcomes of women with gestational diabetes mellitus (GDM), determining risk factors for increased vigilance. SUBJECTS AND METHODS: We studied 924 pregnancies in 916 patients between November 6, 2001 and September 21, 2009. RESULTS: Risk factors were found in 95.1% of cases. The prevalence of maternal diabetes, paternal diabetes and diabetes in other family members was 24.3%, 9.4% and 24.7%, respectively. Predictive factors for insulin use were: screening fasting glucose (FG) ≥ 85, Oral Glucose Tolerance Test (OGTT) FG ≥ 95, 2h glucose after 75 g ≥ 200 mg/dL, previous GDM, obesity, HbA1c > 6%, and the association of risk factors including family history of diabetes mellitus and obesity or previous GDM, the last one the most relevant (p < 0,05). CONCLUSIONS: Risk factors were very sensitive for GDM detection, and provision of family history strengthens its relationship with T2DM. Greater vigilance is recommended for patients with predictive factors for insulin requirement.

The rs10885122 polymorphism of the adrenoceptor alpha 2A (ADRA2A) gene in Euro-Brazilians with type 2 diabetes mellitus

Objective To investigate the association of the rs10885122G>T polymorphism in the ADRA2A gene in a Euro-Brazilian sample of healthy (controls) and type 2 diabetic (T2D) subjects. Subjects and methods We used fluorescent probes (TaqMan) to genotype 241 subjects, that is, 121 healthy and 120 T2D subjects, who were classified based on the Brazilian Diabetes Association (2013) and American Diabetes Association (2014) criteria. Results The genotype and allele frequencies showed no significant (P > 0.05) difference between the two studied groups. The minor allele (T) frequencies (95%CI) for rs10885122 were 19% (14-24%) and 20% (15-26%) for healthy and T2D groups, respectively. Carriers of the T allele (genotypes GT+TT) were significantly associated (P = 0.016) with approximately a 7-kg body weight reduction compared with the genotype GG, which was only found in the T2D group. Conclusion The rs10885122G>T polymorphism of the ADRA2A gene was not associated with T2D in Euro-Brazilians, and carriers of the T allele had lower body weight in the presence of T2D. Arch Endocrinol Metab. 2015;59(1):29-33 .

RAGE receptor and its soluble isoforms in diabetes mellitus complications / O receptor RAGE e suas isoformas solúveis nas complicações do diabetes mellitus

Chronic hyperglycemia, which is present in all types of diabetes, increases the formation of advanced glycation end-products (AGEs). The interaction of AGEs with receptor of advanced glycation end-products (RAGE) initiates a cascade of pro-inflammatory and pro-coagulant processes that result in oxidative stress, stimulating the formation and accumulation of more AGE molecules. This cyclic process, denominated metabolic memory, may explain the persistency of diabetic vascular complications in patients with satisfactory glycemic control. The RAGE found in several cell membranes is also present in soluble isoforms (esRAGE and cRAGE), which are generated by alternative deoxyribonucleic acid splicing or by proteolytic cleavage. This review focuses on new research into these mediators as potential biomarkers for vascular complications in diabetes.

A hiperglicemia crônica, presente em todas as formas de diabetes, favorece a formação de produtos finais de glicação avançada (AGEs). A interação de AGEs com o receptor de produtos finais glicosilados (RAGE) inicia uma cascata de processos pró-inflamatórios e pró-coagulantes que resultam em estresse oxidativo, o qual estimula a formação e o acúmulo de maior quantidade de moléculas de AGEs. Esse processo cíclico, denominado memória metabólica, pode explicar por que, mesmo após um período de bom controle glicêmico, as complicações vasculares associadas ao diabetes não regridem. O RAGE fixado nas membranas de várias células também está presente em isoformas solúveis (esRAGE e cRAGE), geradas por processamento alternativo do ácido desoxirribonucleico (DNA) ou por clivagem proteolítica. Esta revisão aborda os novos estudos sobre a função desses mediadores como potenciais biomarcadores para as complicações vasculares no diabetes.

Marcadores para o diagnóstico e tratamento de 924 gestações com diabetes melito gestacional / Markers of diagnosis and treament in 924 pregnancies with gestational diabetes mellitus

OBJETIVOS: Avaliar o perfil epidemiológico e a evolução de mulheres com diabetes melito gestacional (DMG), determinando fatores de risco para maior vigilância. SUJEITOS E MÉTODOS: Foram estudadas 924 gestações de 916 pacientes, de 6 de novembro de 2001 a 21 de setembro de 2009. RESULTADOS: Foram encontrados fatores de risco para DMG em 95,1 por cento dos casos. A prevalência de diabetes materno, paterno e em outros familiares foi de 24,3 por cento, 9,4 por cento e 24,7 por cento, respectivamente. Os fatores preditivos para uso de insulina foram: glicemia de jejum (GJ) no rastreamento ≥ 85, GJ no Teste Oral de Tolerância à Glicose (TOTG) ≥ 95, glicemia 2h após 75 g de glicose ≥ 200 mg/dL, DMG prévio, obesidade, HbA1c > 6 por cento e história familiar de DM em parente de primeiro grau associada à obesidade ou DMG prévio, esta última a associação mais relevante (p < 0,05). CONCLUSÕES: Os fatores de risco analisados se mostraram altamente sensíveis para a detecção de DMG, e a disposição da história familiar reforça sua relação com o DM2. Recomenda-se maior vigilância a gestantes com fatores preditivos para necessidade de insulina.

OBJECTIVES: To evaluate the epidemiological profile and outcomes of women with gestational diabetes mellitus (GDM), determining risk factors for increased vigilance. SUBJECTS AND METHODS: We studied 924 pregnancies in 916 patients between November 6, 2001 and September 21, 2009. RESULTS: Risk factors were found in 95.1 percent of cases. The prevalence of maternal diabetes, paternal diabetes and diabetes in other family members was 24.3 percent, 9.4 percent and 24.7 percent, respectively. Predictive factors for insulin use were: screening fasting glucose (FG) ≥ 85, Oral Glucose Tolerance Test (OGTT) FG ≥ 95, 2h glucose after 75 g ≥ 200 mg/dL, previous GDM, obesity, HbA1c > 6 percent, and the association of risk factors including family history of diabetes mellitus and obesity or previous GDM, the last one the most relevant (p < 0,05). CONCLUSIONS: Risk factors were very sensitive for GDM detection, and provision of family history strengthens its relationship with T2DM. Greater vigilance is recommended for patients with predictive factors for insulin requirement.