Phenotype and predictors of insulin independence in adults presenting with diabetic ketoacidosis: a prospective cohort study.

AIMS/HYPOTHESIS: The aim of this work was to describe the phenotype of adults presenting with a first episode of diabetic ketoacidosis (DKA) in Cape Town, South Africa, and identify predictors of insulin independence at 12 and 60 months after presentation. METHODS: A prospective, descriptive cohort study of all individuals, 18 years or older, presenting for the first time with DKA to four public-sector hospitals of the Groote Schuur Academic Health Complex was performed. Clinical, biochemical and laboratory data including GAD antibody and C-peptide status were collected at baseline. Insulin was systematically weaned and stopped in individuals who achieved normoglycaemia within the months after DKA. Individuals were followed for 12 months and then annually until 5 years after initial presentation with ketoacidosis. RESULTS: Eighty-eight individuals newly diagnosed with diabetes when presenting with DKA were included and followed for 5 years. The mean ± SD age was 35±10 years and the median (IQR) BMI at diagnosis was 28.5 (23.3-33.4) kg/m2. Overall, 46% were insulin independent 12 months after diagnosis and 26% remained insulin independent 5 years after presentation. Forty-one participants (47%) tested negative for anti-GAD and anti-IA-2 antibodies and had C-peptide levels >0.3 nmol/l; in this group, 68% were insulin independent at 12 months and 37% at 5 years after diagnosis. The presence of acanthosis nigricans was strongly associated with insulin independence (OR 27.1 [95% CI 7.2, 102.2]; p<0.001); a positive antibody status was associated with a lower likelihood of insulin independence at 12 months (OR 0.10 [95% CI 0.03, 0.36]; p<0.001). On multivariable analysis only acanthosis (OR 11.5 [95% CI 2.5, 53.2]; p=0.004) was predictive of insulin independence 5 years after diagnosis. CONCLUSIONS/INTERPRETATION: The predominant phenotype of adults presenting with a first episode of DKA in Cape Town, South Africa, was that of ketosis-prone type 2 diabetes. These individuals presented with obesity, acanthosis nigricans, negative antibodies and normal C-peptide and could potentially be weaned off insulin at follow-up. Classic type 1 diabetes (lower weight, antibody positivity, low or unrecordable C-peptide levels and long-term insulin dependence) was less common. The simple clinical sign of acanthosis nigricans is a strong predictor of insulin independence at 12 months and 5 years after initial presentation.

Impact of Diabetes Mellitus Following Tonsillectomy in Adults: A National Surgical Quality Improvement Program Analysis.

OBJECTIVES: To identify 30-day complication rates specific to patients with diabetes mellitus following tonsillectomy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients undergoing tonsillectomy between 2005 and 2018. Patients were stratified into 3 cohorts: insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), and non-diabetes mellitus (NODM). Coarsened-exact-matching was utilized to account for baseline differences between cohorts. Outcomes studied included post-operate complications, prolonged hospitalization, and unplanned readmissions. RESULTS: A total of 986 DM and 26 774 NODM patients were included, and the mean age of patients undergoing tonsillectomy was 29.5 ± 11.6 and 28.7 ± 11.0 years, respectively. The majority of patients were female (70.5% for both DM and NODM cohorts) and White/Caucasian (89.2% vs 89.3%). Among patients undergoing tonsillectomy, a greater proportion of DM patients experienced an operative time greater than or equal to the 75th percentile (35 minutes; 25.9% vs 22.8%, P = .024), overall morbidity (12.6% vs 5.4%, P < .001), pneumonia (0.6% vs 0.2%, P = .036), and reoperation (10.2% vs 3.5% P < .001) in comparison to NODM patients. In an analysis between IDDM (n = 379) and NIDDM (n = 211) patients, IDDM patients were at an increased risk for prolonged hospitalization (1.4% vs 0.0%, P = .045), pneumonia (5.2% vs 0.5%, P < .001), urinary tract infections (3.3% vs 0.3% P = .004), major complications (15.6% vs 7.7%, P = .002), minor complications (19.9% vs 8.2%, P < .001), and overall complications (10.0% vs 1.3%, P < .001). CONCLUSION: DM patients are at a heightened risk for complications following tonsillectomy. Standardized protocols, careful pre-operative planning, and stringent glycemic management may help optimize patient outcomes.

The effect of insulin dependent diabetes on bone metabolism and growth after spinal fusion.

STUDY DESIGN: Experimental animal model. OBJECTIVE: The purpose of this study was to evaluate the hypothesis that insulin dependent diabetes mellitus (IDDM) will inhibit the formation of a solid bony union after spinal fusion surgery via an alteration of the microenvironment at the fusion site in a rat model. SUMMARY OF BACKGROUND DATA: Previous studies report diabetes mellitus (DM) and specifically IDDM as a risk factor for complications and poor surgical outcomes following spinal fusion. METHODS: Twenty control and 22 diabetic rats were obtained at 5 weeks of age. At 20 weeks of age, all animals underwent posterolateral lumbar fusion surgery using a tailbone autograft with diabetic rats receiving an implantable time release insulin pellet. A subset of rats was sacrificed 1-week postsurgery for growth factor (PDGF, IGF-I, TGF-ß, and VEGF) and proinflammatory cytokine ELISA analysis. All other rats were sacrificed 3-months postsurgery for fusion evaluation via manual palpation and micro CT. Glycated hemoglobin (HbA1c) was measured at surgery and sacrifice on all animals. RESULTS: Compared with healthy rats undergoing spinal fusion, rats with IDDM demonstrated a significant reduction in manual palpation fusion rates (16.7% vs. 43%, p<.05). Average bone mineral density, bone volume, and bone volume fraction were also significantly reduced and negatively correlated to blood glucose levels. IL-1B, IL-5, IL-10, TNF-α, and KC/GRO were significantly elevated in fusion beds of IDDM rats. CONCLUSIONS: This study demonstrates that rats with IDDM demonstrate a reduced rate and quality of spinal fusion with increased local levels of inflammatory cytokines. Targeted modalities are required to improve bone healing in this growing, high-risk population. CLINICAL SIGNIFICANCE: This is the first translational animal model of IDDM to evaluate the rate and quality of spinal fusion while controlling for other surgical and patient-related risk factors. Our findings demonstrate the complex nature by which IDDM impairs bone healing and highlight the need for additional basic science research to further elucidate this mechanism in order to develop more effective therapeutic interventions.

Carriers of the TCF7L2 rs7903146, rs12255372 Risk Alleles in the South Tamil Nadu T2DM Patients Present with Early Incidence and Insulin Dependence.

BACKGROUND AND AIMS: Metabolic abnormalities in T2DM (Type 2 diabetes mellitus) include classic manifestations such as impaired insulin secretion, synthesis and peripheral insulin resistance. The intronic variants rs7903146 and rs12255372 of the TCF7L2 (transcription factor 7-like 2) gene are strongly associated with risk of incidence of T2DM and impaired ß-cell functions. Studies addressing the early T2DM onset, and early insulin dependence in T2DM patients of south Tamil Nadu are still lacking, and hence the present study focuses in determining the influence of the TCF7L2 polymorphisms in the incidence and disease course in the T2DM patients of south Tamil Nadu. METHODS: Anthropometric measurements and biochemical parameters were carried out in early onset (Group A), early onset insulin dependent T2DM patients (Group B) and non-insulin dependent T2DM patients (Group C). PCR, allele specific PCR (ASP), PCR product sequencing strategies were utilized to determine the genotype and the impact of the TCF7L2 SNPs in the T2DM disease course. RESULTS: Female T2DM patients with the CT/TT rs7903146 genotype (P = 0.005) and the rs12255372 GT/TT genotype (P = 0.036) exhibited a significantly low mean age for T2DM incidence. Correlation/regression analysis in the T2DM patients revealed that rs12255372 (P = 0.042) is associated with early onset in the Group C patients and the rs7903146 (P = 0.018), rs12255372 (P = 0.026) are associated with insulin dependence in the group B patients. CONCLUSION: Screening for the TCF7L2 polymorphisms will prevent T2DM incidence and enable life style changes, appropriate therapeutic strategies that would help combat the accelerated disease course in the T2DM patients.

Ketosis-Prone Diabetes (Flatbush Diabetes): an Emerging Worldwide Clinically Important Entity.

PURPOSE OF REVIEW: Ketosis-prone diabetes or Flatbush diabetes has been widely recognized as a clinical entity since 1984. Most of the early clinical studies focused on African American or Afro-Caribbean individuals. It is now being recognized as an important clinical entity in sub-Saharan Africans, Asian and Indian populations, and Hispanic populations. Major questions remain as to its pathogenesis and whether it is a unique type of diabetes or a subset of more severe type 2 diabetes with greater loss of insulin action in target tissues. This review summarizes the main clinical and mechanistic studies to improve the understanding of ketosis-prone (Flatbush) diabetes. RECENT FINDINGS: Little data are available on the magnitude of KPD in the different susceptible populations. It is relatively common in black populations. KPD is defined as a syndrome in which diabetes commences with ketoacidosis in individuals who are GAD and anti-islet cell antibody negative and have no known precipitating causes. The patients present during middle age, are overweight or mildly obese, and in many reports are more likely to be male. After intensive initial insulin therapy, many patients become insulin independent and can be well controlled on diet alone or diet plus oral medications. The clinical course of KPD is like that of patients with type 2 diabetes rather than that of type 1 diabetes. Little differences are found in the clinical characteristics and clinical outcomes between patients presenting with KPD and those presenting with severe hyperglycemia with no ketoacidosis. The mechanisms responsible for the development of ketosis-prone diabetes as well its remission remain unknown.

FITC-labeled d-glucose analog is suitable as a probe for detecting insulin-dependent glucose uptake.

The detection of the insulin-dependent glucose uptake is a vital part in the research of diabetes. To establish a sensitive assay for measuring glucose uptake in living cells, we synthesized a FITC linked d-glucosamine 2 as a probe. 2 was obtained by the reaction of commercially available d-glucosamine hydrochloride and FITC and was determined as a single anomeric form by 1H NMR and 13C NMR. 2 exhibited good water solubility and stability. An uptake assay in HepG2 cells with or without insulin demonstrated that FITC showed strong cellular uptake, whereas uptake of 2 is much less but is insulin dependent. This suggests that 2 is specifically transported into cells through a receptor that is regulated by insulin and has potential application in screening of compounds or genes that regulate the insulin-dependence in cell-based assays.

A COMMENTARY ON CLASSIFICATION OF DIABETES: LATENT AUTOIMMUNE DIABETES IN ADULTS (LADA) OR INTERMEDIARY DIABETES MELLITUS (IDM)?

Diabetes Mellitus is a huge syndrome which can be detected from the first day of life until the last year of life of a centenarian. In the current classification of diabetes among the so-called "idiopathic phenotypes", apart Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D) has been included provisionally term "Latent Autoimmune Diabetes in Adults" (LADA). This has unclear characterization regarding the age at onset, the presence of anti-ß-cell antibodies and the level of insulin secretory function, in conformity with C-peptide levels. According to several recent publications, there are no specific biochemical or genetic markers for Latent Autoimmune Diabetes in Adults (LADA), but only a gradual transition from T1D to T2D. In addition, the word "latent" in the construction of "LADA" term is inaccurate because in this phenotype nothing is latent: both the autoimmunity and diabetes are present and are even parts of the diagnosis. So that, the best term should be what in reality this sub-phenotype is: an Intermediary Diabetes Mellitus (IDM). Some recent genetic data strongly support this designation.

The impact of bariatric surgery on insulin-treated type 2 diabetes patients.

INTRODUCTION: Bariatric surgery has been shown to lead to significant improvement in glucose homeostasis, resulting in greater rates of type 2 diabetes mellitus (T2DM) remission. While there is substantial evidence of the benefits of bariatric/metabolic surgery in obese diabetic patients on oral therapy (O-T2D), more evidence is necessary in the case of insulin-treated type 2 diabetes (I-T2D) patients and the selection of surgical procedure. METHODS: Analysis of the Ontario Bariatric Registry data was performed, comparing outcomes of Roux-en-Y-gastric bypass (RYGB) and sleeve gastrectomy (SG) on insulin-treated versus non-insulin-treated T2DM patients. We compared weight loss, medication use and remission rates during a 3-year follow up. RESULTS: A total of 3668 diabetic Bariatric Registry patients underwent surgery from Jan 2010 to Feb 2017, across 7 Bariatric Centers of Excellence in Ontario. Of these 2872 were O-T2D and 1187 were I-T2D. Weight loss was similar between the two groups at 3 years; with mean %WL of 30.1% for the insulin group vs. 28.3% non-insulin (p = 0.0673). At 3 years, 11.3% of the non-insulin and 59.6% of the insulin-dependent group were using anti-diabetic medication (p < 0.0001). Among insulin-dependent patients, RYGB showed greater reduction in insulin use with 26.5 and 40% compared to SG at 3 years. O-T2D patients experienced more complete diabetes remission, with 66.5 vs. 18.5% (p < 0.0001) at 3 years. Complete remission for I-T2D patients was higher in the RYGB group than SG (p < 0.0001) at years 1 and 2 (8.5 vs. 5.4% and 24.4 vs. 21.1%). The same trend was found regardless of insulin use; complete remission higher for RYGB at 1 and 2 years [50.7 vs. 39.8% (p < 0.0001), and 54.6 vs. 49.1% (p < 0.0001)]. CONCLUSION: While both RYGB and SG procedures provide effective treatment for I-T2D patients in terms of weight loss and diabetes, incidence of complete remission for insulin-dependent patients is higher with RYGB in earlier years.

The impact of insulin dependence on short-term postoperative complications in diabetic patients undergoing total shoulder arthroplasty.

BACKGROUND: The number of total shoulder arthroplasty (TSA) procedures performed is steadily increasing, and it is important to characterize predictors of postoperative complications for risk assessment models. Whereas diabetes has been associated with increased morbidity after TSA, the impact of insulin dependence on the risk profile of diabetic patients has not been described. METHODS: The National Surgical Quality Improvement Program database from 2011-2014 was used to identify 5918 TSA cases. Patients were categorized as non-diabetes mellitus (non-DM), non-insulin-dependent diabetes mellitus (NIDDM), or insulin-dependent diabetes mellitus (IDDM). Thirty-day postoperative complication rates, length of stay (LOS), and readmission rates were compared across the diabetes groups. Multivariable logistic regression adjusting for demographics and comorbidity burden was performed to determine the independent association between insulin dependence and postoperative outcomes. RESULTS: In bivariate analysis, NIDDM and IDDM were associated with multiple postoperative complications, including stroke, sepsis, wound complications, blood transfusion, and extended LOS. With multivariable logistic regression, however, NIDDM patients did not have significantly greater odds of any study end point relative to non-DM patients. IDDM patients had significantly greater odds for having any postoperative complication (odds ratio [OR], 1.53), stroke (OR, 13.63), blood transfusion (OR, 1.67), and extended LOS (OR, 1.38). CONCLUSIONS: After adjustment for demographics and comorbidity burden, NIDDM patients had risk profiles similar to those of non-DM patients. IDDM was an independent predictor of multiple postoperative complications. Insulin dependence should be considered in the preoperative risk assessment of diabetic patients undergoing TSA.

Insulin Dependence Increases the Risk of Failure After Total Knee Arthroplasty in Morbidly Obese Patients.

UNLABELLED: The aims of this study were to compare the outcomes between nondiabetic (n=1284), type II diabetic (n=530), and insulin-dependent type II diabetic (n=164) morbidly obese (body mass index ≥40 kg/m(2)) patients undergoing primary total knee arthroplasty at 6-year follow-up. Patients with type II diabetes mellitus (DM) had similar outcomes when compared with non-DM patients. However, patients with insulin dependence had an increased risk of reoperation (hazard ratio [HR], 1.8; P=.005), revision (HR, 2; P=.02), and periprosthetic joint infection (HR, 2.1; P=.03), as well as decreased 10-year implant survivorship (84% vs 92%; P=.01) when compared to non-DM patients. Prospective studies should further evaluate outcomes and optimization measures within this population. LEVEL OF EVIDENCE: Level III-prognostic study.

Factors associated with early relapse to insulin dependence in unprovoked A-ß+ ketosis-prone diabetes.

OBJECTIVE: Unprovoked "A-ß+" Ketosis-Prone Diabetes (KPD), a unique diabetic syndrome of adult-onset, obesity and proneness to ketoacidosis, is associated with rapid recovery of ß cell function and insulin-independence. Whereas most patients experience prolonged remission, a subset relapses early to insulin dependence. We sought to define factors associated with early relapse. METHODS: We utilized a prospective, longitudinal database to analyze 50 unprovoked A-ß+ KPD patients with >2 measurements of ß cell function and glycemia following baseline assessment. RESULTS: 19 patients (38%) relapsed to insulin dependence <1 year after the index DKA episode, while 31 (62%) remained insulin-independent for >1 year (median 4.2 years). Younger age at baseline (OR=0.947, P=0.033), and lower HOMA2-%ß (OR=0.982, P=0.001), lower HOMA2-IR (OR=0.582, P=0.046) and higher HbA1c at 1 year (OR=1.71, P=0.002) were associated with early relapse. A multivariate model with these variables and the interaction of HOMA2-%ß and HbA1c at 1 year provided a good fit (P<0.05). CONCLUSIONS: Relapse to insulin dependence in unprovoked A-ß+ KPD patients is associated with younger age and, after 1 year, lack of robust increase in ß cell functional reserve, and suboptimal glycemic control. Measurements of these parameters 1 year after the index DKA episode can be used to assess the need for insulin therapy.

Association between diabetes and amyotrophic lateral sclerosis in Sweden.

BACKGROUND AND PURPOSE: Energy metabolism is altered in patients with amyotrophic lateral sclerosis (ALS) but the role of diabetes is largely unknown. METHODS: A population-based case-control study was conducted of 5108 ALS cases and 25,540 individually matched population controls during 1991-2010. Information on ALS and pre-existing diabetes was retrieved from the Swedish Patient Register to explore the association of ALS with diabetes overall and with insulin-dependent or non-insulin-dependent diabetes specifically. Variation of the association by diabetes duration and age was also studied. RESULTS: In total, 224 ALS cases (4.39%) and 1437 controls (5.63%) had diabetes before the index date, leading to an overall inverse association between diabetes and ALS risk [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.68-0.91]. The association was strong for non-insulin-dependent diabetes (OR 0.66, 95% CI 0.53-0.81) but not for insulin-dependent diabetes (OR 0.83, 95% CI 0.60-1.15) and varied as a function of diabetes duration, with the strongest association observed around 6 years after first ascertainment of diabetes. The association was age-specific; the inverse association was noted only amongst individuals aged 70 or older. In contrast, for younger individuals (<50 years), pre-existing insulin-dependent diabetes was associated with a higher ALS risk (OR 5.38, 95% CI 1.87-15.51). CONCLUSIONS: Our study suggests that there is an association between diabetes and ALS, and highlights the importance of taking into account age, insulin dependence and diabetes duration. Future studies should explore whether the association is independent of body mass index.

Phenotypic heterogeneity of latent autoimmune diabetes in adults identified by body composition analysis.

BACKGROUND: In patients with Latent Autoimmune Diabetes in Adults (LADA) a lower body mass index was reported compared with classical type 2 diabetes (T2D), and was found to be associated with a faster progression to insulin-dependence. In this study we determined the body composition in a cohort of LADA patients from Sardinia, Italy, and compared it with age- and gender-matched patients diagnosed as having adult-onset type 1 diabetes (T1D) and non-autoimmune T2D. METHODS: In 210 LADA patients, 210 T2D patients and 30 adult-onset T1D patients of Sardinian origin we assessed total and segmental body composition (weight-adjusted percent fat mass and lean mass) by using Dual Energy X-rays Absorptiometry (DXA). RESULTS: In the whole cohort of LADA patients total fat mass was significantly smaller compared with T2D patients (p < 0.0001), while no difference was found between LADA and T1D patients. In LADA men fat depletion involved all body segments, while in LADA women it was observed only in the truncal segment (p < 0.0001), as in the upper and lower regions fat deposits were larger compared to T2D (p < 0.0001). However, LADA women showed a significantly elevated truncal fat compared to T1D women (p < 0.004), whereas no difference was detected in the extremities. CONCLUSIONS: Body composition in LADA patients shows substantial difference, in a gender-dependent way, compared to classic T2D. In women fat deposits tend to accumulate in peripheral regions rather than centrally, whereas in men the distribution is more homogeneous. In addition, central fat depletion in LADA women appears to be a significant predictor of faster progression to insulin dependence. Thus, routine assessment of body composition may help the physician identify LADA patients who require early insulin treatment in order to delay beta-cell exhaustion, as well those with increased CV risk due to excess truncal adiposity.

Mastopatia Diabética: una entidad infrecuente a diferenciar / Diabetic mastitis: an uncommon entity differentiate

Introducción: La Diabetes mellitus produce microvasculitis y alteración histoarquitectural de la mama. Se encuentra en el 1% de la mastopatía benigna. Sin embargo, la distorsión delparénquima produce sintomatología inflamatoria clínicamente similar a las mastopatías inflamatorias infecciosas. Su diagnóstico imagenológico, es a su vez, de gran dificultad interpretativa. Estos parámetros inespecíficos, desembocan a tratamientos que no logran eficacia en la enfermedad, más aún si se ignora el contexto de la enfermedad de origen, la cual essistémica. Objetivos: destacar la importancia del diagnóstico diferencial de esta infrecuente entidad patológica. Material y Métodos: se revisaron historias clínicas de un servicio de mastología por el término de seis meses, a efectos de recabar información estadística. Resultados: histológicamente, estas pacientes presentaron rasgos microscópicos que consisten en una lobulitis linfocitaria que afecta al epitelio y gran vasculitis edematosa. El diagnóstico histológico es crucial para llegar al tratamiento. Conclusiones: la mastopatía de las pacientes diabéticas insulinodependientes es la manifestación crónica de eventos sistémicos, producido en un porcentaje muy bajo de pacientes con la enfermedad. La correcta interpretación clínica y mamográfica, además de la sospecha semiológica desembocanen el adecuado tratamiento de esta enfermedad, inserta en un contexto sistémico.

Introduction: Diabetes mellitus occurs histoarquitectural microvasculitis and alteration of the breast. It is found in 1% of benign breast disease . However, distortion occurs parenchymal inflammatory symptoms clinically similar to infectious inflammatory breast disease. Its diagnostic imaging , is in turn highly interpretive difficulty. These non specific parameters lead to effective treatments that fail in the disease , especially if the context of disease origin is unknown, which is systemic. Objectives: To highlight the importance of the differential diagnosis of this rare disease entity. Material and Methods : Clinical histories mastology service for a period of six months for the purpose of collecting statistical data were reviewed.Results: Histologically , these patients had microscopic features consisting lobulitis lymphocytic affecting large edematous epithelium and vasculitis. Histological diagnosis is crucial to get the treatment. Conclusions: Diabetic mastopathy in insulin dependent patients is chronic manifestation of systemic events , produced in a very low percentage of patients with the disease. The correct clinical and mammographic interpretation, in addition to lead to suspicion semiológica proper treatment of this disease, inserted in a systemic context.

Trastornos metabólicos asociados con la evolución hacia la diabetes mellitus tipo 2 en una población en riesgo / Metabolic disorders associated with the evolution to type 2 diabetes mellitus in a risk group

INTRODUCCIÓN: el estado clínico y metabólico de la población en riesgo de padecer diabetes mellitus tipo 2 (DM2) es muy heterogéneo. OBJETIVO: identificar los factores que influyen en la progresión hacia la diabetes en los subgrupos de pacientes con distintos tipos y gravedad de los trastornos metabólicos. MÉTODOS: se realizó un estudio prospectivo en 209 sujetos en alto riesgo de progresión hacia la diabetes mellitus tipo 2 (antecedentes de trastornos de la tolerancia a la glucosa sin hiperglucemia en ayunas) para examinar los trastornos metabólicos que se asocian con la progresión hacia la diabetes. Se estudió la tolerancia a la glucosa, la secreción de insulina y la sensibilidad a la insulina al inicio del estudio y 2 años después. RESULTADOS: se encontró que el riesgo de desarrollo de diabetes mellitus dependía significativamente del grado de deterioro de la tolerancia a la glucosa presente en el estudio inicial (tolerancia a la glucosa normal, 10 por ciento; tolerancia a la glucosa alterada, 14,6 por ciento; tolerancia a la glucosa alterada + glucemia en ayunas alterada, 56,7 por ciento). En el grupo con tolerancia a la glucosa normal el factor predictivo fundamental de evolución hacia la diabetes mellitus era la deficiencia de la respuesta insulinosecretora inicial (OR: 8,13; IC de 95 por ciento; 1,83 a 36,0). En los sujetos con tolerancia a la glucosa alterada con glucemia en ayunas alterada y sin esta, el factor determinante era la glucemia en ayunas (OR: 5,41; IC de 95 por ciento; 2,15 a 13,6). La resistencia a la insulina no fue un factor predictivo significativo en ninguno de los subgrupos estudiados. CONCLUSIONES: los trastornos de la glucemia posprandial en las etapas iniciales de la evolución de la diabetes mellitus tipo 2 son inconstantes o reversibles, y no son suficientes para basar su diagnóstico precoz y las actividades preventivas o terapéuticas. La aparición de glucemia en ayunas alterada marca el inicio de una etapa de progresión acelerada hacia la diabetes mellitus tipo 2, por lo que en este grupo es necesario intensificar las medidas para revertir o enlentecer el deterioro metabólico. En el grupo con alto riesgo de diabetes y tolerancia a la glucosa normal, el único factor metabólico identificado como marcador pronóstico de la progresión hacia la diabetes es la baja respuesta insulínica. Se recomienda incorporar la evaluación de la capacidad funcional de la célula beta para la detección precoz de personas en riesgo de padecer diabetes(AU)

INTRODUCTION: The clinical and metabolic state of persons in risk of suffer type 2 diabetes mellitus (DM2) is very heterogeneous. Objetive: to identify the factors influencing in progression to diabetes in subgroups of patients with different types and the severity of metabolic disorders. A prospective study was conducted in 209 subjects in high risk of progression to type 2 diabetes mellitus (backgrounds of disorders related to glucose tolerance without fasting hyperglycemia) to examine the metabolic disorders associating with progression to diabetes. Glucose tolerance, insulin secretion and insulin sensitivity were studied at onset and two years later. RESULTS: we found that the risk to develop diabetes mellitus was in a significant dependence of the deterioration degree of glucose tolerance present in the initial study (normal glucose tolerance, 10 percent; altered glucose tolerance, 14,6 percent; altered glucose tolerance + altered fasting glycemia, 56,7 percent). In the group with a normal glucose tolerance the fundamental predictive factor of evolution to diabetes mellitus was the failure of initial insulin secretory response (OR: 8,13; 95 percent CI; 1,83 to 36,0). In the subjects with altered glucose tolerance with fasting altered glycemia and without it, determinant factor was the fasting glycemia (OR: 5,41; 95 percent CI; 2,15 to 13,6). The insulin resistance was not a significant predictive factor in any study subgroups. CONCLUSIONS: postprandial glycemia disorders in early stages of evolution to type 2 diabetes mellitus are changeable or reversible and insufficient to base its early diagnosis and the preventive or therapeutical activities. Appearance of an altered fasting glycemia is the onset of an accelerated progression stage to type 2 diabetes mellitus, thus, in this group it is necessary to intensify the measures to revert or slow the metabolic deterioration. In group with a high risk of diabetes and a normal glucose tolerance the only metabolic factor identified as a prognostic marker of progression to diabetes is the poor insulin-response. It is recommended to add the assessment of the functional ability of Beta-cell for the early detection of persons in risk of diabetes(AU)