Presencia de autoanticuerpos anti islotes pancreáticos en diabetes tipo 1 durante la edad pediátrica / Presence of anti-pancreatic islet autoantibodies in type 1 diabetes in children

En la Diabetes tipo 1 (DM1) la pérdida de células ß pancreáticas es consecuencia de un proceso de autoinmunidad que cursa con la presencia de autoanticuerpos anti-islotes pancreáticos (AAPs). Estos AAPs son marcadores útiles para la clasificación de la enfermedad. En un centro pediátrico de tercer nivel se analizó la frecuencia de presentación de GADA, IA-2A, ZnT8A e IAA en un grupo con reciente debut entre enero 2018 y agosto 2021 (n= 90). Además, se investigó la frecuencia de presentación y relación de los AAPs con la edad, sexo y tiempo de evolución en pacientes en seguimiento (n= 240). En el grupo de debut se obtuvo positividad de GADA, IA-2A, ZnT8A y IAA en 77,8; 60; 62 y 47,8% de los pacientes respectivamente, un 4% no presentó AAPs. El 95,6% de los pacientes presentaron al menos un AAPs positivo. La frecuencia de IAA en el grupo en debut fue mayor en menores de 5 años. En el grupo en seguimiento el 75,2% resultaron GADA positivo (85,7% en mujeres y 62,8% en varones) p<0,05. IA-2A y ZnT8A fueron positivos en 45 y 51.7% respectivamente. El 91% presentaron al menos un AAP positivo. En este grupo se evidenció una menor positividad en función del tiempo de evolución. Se pudo determinar la frecuencia de presentación de los AAPs en un grupo en debut y la relación con la edad, sexo y tiempo de evolución en pacientes en seguimiento. La determinación de APPs facilita la correcta clasificación y elección de la terapia adecuada (AU)

In type 1 diabetes (DM1) the loss of pancreatic ß-cells is a consequence of an autoimmune process that results in the presence of pancreatic anti-islet autoantibodies (PAAs). PAAs are useful markers for the classification of the disease. The frequency of presentation of GADA, IA-2A, ZnT8A, and IAA in a group with recent debut seen between January 2018 and August 2021 (n= 90) was analyzed in a tertiary pediatric center. In addition, we investigated the frequency of presentation and association of PAAs with age, sex, and time of evolution in patients in follow-up (n= 240). In the debut group, GADA, IA2A, ZnT8A, and IAA positivity was found in 77.8, 60, 62, and 47.8% of patients, respectively; no PAAs were observed in 4% of the patients. Overall, 95.6% presented at least one positive PAA. The frequency of IAA in the debut group was higher in children younger than 5 years. In the follow-up group, 75.2% were GADA positive (85.7% of females and 62.8% of males) p<0.05. IA-2A and ZnT8A were positive in 45 and 51.7% respectively. Ninety-one percent presented with at least one positive PAA. In this group, a lower positivity was evidenced as a function of the time of evolution. The frequency of presentation of PAAs in a debut group and the relationship with age, sex, and time of evolution in patients in follow-up was demonstrated. The assessment of PAAs facilitates the correct classification and choice of adequate therapy (AU)

A insulina regula as vias de sinalização induzidas por LPS em macrófagos derivados de medula óssea / Insulin regulates LPS-induced signaling pathways in macrophages derived from bone marrow

Pacientes diabéticos apresentam alterações no sistema imunológico que promovem, em parte, maior suscetibilidade de infecções bacterianas. O tratamento com insulina melhora a sobrevida e reduz o número de infecções recidivas no paciente com diabetes mellitus do tipo 1 (DM1). Pouco se sabe sobre os efeitos do diabetes e a ação da insulina nos macrófagos. Neste trabalho, investigamos a proteína fosfatidilinositol-3-quinase (PI3K), proteína quinase B (Akt) e as quinases ativadas por mitógenos (MAPK) em macrófagos derivados de medula óssea (BMDM) e sua participação no estímulo por lipopolissacarídeo (LPS) na presença ou não do tratamento com insulina através da secreção dos mediadores inflamatórios fator de necrose tumoral (TNF)-α, interleucina (IL)-6 e IL-10. Observamos que os BMDM de animais com DM1 apresentam aumento da expressão da subunidade catalítica PI3K p110alpha com redução na subunidade reguladora PI3K p55 e maior expressão da fosforilação das proteínas Akt (Serina-473 e Treonina-308), quinase regulada por sinal extracelular (ERK) 1/2 e quinase ativada por estresse/quinase Jun-amino-terminal (SAPK/JNK) MAPK. Observou-se alteração na concentração das citocinas TNF-α, IL-6 e IL-10 no sobrenadante da cultura de BMDM dos animais diabéticos após estímulo com LPS, menor taxa de metabolismo mitocondrial, no entanto, sem resultar em morte celular, tampouco na expressão do receptor do tipo Toll 4 na membrana celular. Já o reestímulo destas células com LPS promoveu aumento na concentração de TNF-α sem alteração das demais citocinas. Além disto, o tratamento com insulina, simultaneamente ao estímulo com LPS, dos BMDM oriundos de animais diabéticos aumentou a concentração de TNF-α, IL-6, da fosforilação de p38, ERK 1/2 e SAPK/JNK MAPK, PI3K p55 e da Akt (Serina-473), o que não ocorreu nos BMDM dos animais não diabéticos sob a mesma condição. Este efeito foi abolido pela inibição farmacológica da PI3K e da ERK 1/2, resultando em novo aumento da concentração de TNF-α e IL-6. A análise conjunta destes resultados indica que a insulina, através da modulação das vias PI3K, Akt, ERK 1/2 e SAPK/JNK, amplifica o aumento da concentração de TNF-α e IL-6 sob estímulo com LPS

Diabetic patients present alterations in the immune system that promote in part a greater susceptibility of bacterial infections. Insulin treatment improves survival and reduces the number of recurrent infections in patients with type 1 diabetes mellitus (DM1). Little is known about the effects of diabetes and the action of insulin on macrophages. In this work we investigated the phosphatidylinositol-3-kinase (PI3K) / protein kinase B (Akt) and mitogen-activated kinase (MAPK) proteins in bone marrow-derived macrophages (BMDM) and their participation in lipopolysaccharide (LPS) or treatment with insulin through the secretion of inflammatory mediators tumor necrosis factor (TNF) -α, interleukin (IL) -6 and IL-10. We observed that BMDM of animals with DM1 increased PI3K p110alpha catalytic subunit expression with a reduction in the PI3K p55 regulatory subunit and increased expression of the phosphorylation of the Akt (Serine-473 and Threonine-308), extracellular signal regulated kinase (ERK) 1/2 and Jun-amino-terminal stress-kinase / kinase (SAPK / JNK) MAPK. Changes in the concentration of TNF-α, IL-6 and IL-10 cytokines in the supernatant of the BMDM culture of diabetic animals after stimulation with LPS were observed, possibly due to a lower rate of mitochondrial metabolism, however, without resulting in cell death , so little in the expression of the Toll 4 receptor on the cell membrane. The re-stimulation of these cells with LPS promoted an increase in TNF-α concentration without alteration of the other cytokines. In addition, insulin and simultaneously LPS stimulation of BMDM from diabetic animals increased the concentration of TNF-α, IL-6, phosphorylation of p38, ERK 1/2 and SAPK / JNK MAPK, PI3K p55 and Akt (Serine-473), which did not occur in the BMDM of non-diabetic animals under the same condition. This effect was abolished by pharmacological inhibition of PI3K and ERK 1/2, resulting in a further increase in the concentration of TNF-α and IL-6. The analysis of these results indicate that insulin by modulating the PI3K, Akt, ERK 1/2 and SAPK / JNK pathways amplifies the concentration levels of TNF-α and IL-6 under stimulation with LPS

Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

ABSTRACT The aim of the present study was to investigate the bone mineral density (BMD) of patients with type 1 Diabetes mellitus (T1DM). We also assessed the association between osteoprotegerin (OPG) genetic polymorphisms and BMD. Genotyping was performed for 1181G>C and 163A>G OPG polymorphisms by allelic discrimination in 119 patients with T1DM and 161 normoglycemic (NG) individuals, aged 6 to 20 years old. Glycemic control, serum parameters of bone metabolism and BMD were evaluated. T1DM patients showed low BMD, poor glycemic control and decreased total calcium values when compared to controls (p < 0.05). For all the polymorphisms studied, the genotype and allele frequencies in patients with T1DM were not significantly different from the controls. In patients with T1DM, carriers of OPG 1181CC showed higher concentrations of ionized calcium compared to patients with GG+GC genotypes. These results suggest that low BMD is associated with poor glycemic control in T1DM. Despite the lack of a detected association between OPG polymorphisms and BMD in these patients, the increased ionized calcium in those carrying OPG 1181CC suggests a possible increase in osteoclastogenesis, a conclusion that may be supported by the lower BMD observed in these subjects.

Pancreatic beta cell protection/regeneration with phytotherapy

Although currently available drugs are useful in controlling early onset complications of diabetes, serious late onset complications appear in a large number of patients. Considering the physiopathology of diabetes, preventing beta cell degeneration and stimulating the endogenous regeneration of islets will be essential approaches for the treatment of insulin-dependent diabetes mellitus. The current review focused on phytochemicals, the antidiabetic effect of which has been proved by pancreatic beta cell protection/regeneration. Among the hundreds of plants that have been investigated for diabetes, a small fraction has shown the regenerative property and was described in this paper. Processes of pancreatic beta cell degeneration and regeneration were described. Also, the proposed mechanisms for the protective/regenerative effects of such phytochemicals and their potential side effects were discussed.

Embora medicamentos disponíveis atualmente sejam úteis no controle de complicações da Diabetes, complicações aparecem em grande número de pacientes. Considerando-se a fisiopatologia do Diabetes, a prevenção da degeneração de células beta e o estímulo da regeneração endógena de ilhotas será abordagem essencial para o tratamento de diabetes mellitus insulino-dependente. A presente revisão aborda compostos fitoquímicos, cujo efeito é provado na proteção/regeneração de células beta de pâncreas. Entre centenas de plantas que têm sido investigadas para o diabetes, pequena fração tem mostrado propriedade regenerativa, que será descrita neste trabalho. Os processos de degeneração e de regeneração das células beta do pâncrease são descritos. Além disso, mecanismos propostos para efeitos de proteção e regeneração desses compostos fitoquímicos e seus possíveis efeitos colaterais também serão discutidos neste trabalho.

Clinical and laboratory features of youth onset Type 2 diabetes in Jamaica / Características clínicas y de laboratorios en la aparición de la diabetes de Tipo 2 en los jóvenes de Jamaica

OBJECTIVES: To assess the frequency of youth onset Type 2 diabetes mellitus (T2D) in Jamaica and the characteristics of youth with this form of diabetes. METHODS: Patients from two major referral hospitals, diagnosed with diabetes before age 25 years and < 6 years prior to the study, were evaluated. Classification was based on the presence of GAD-65 and IA-2 diabetes autoantibodies (AB), fasting (FCP) and stimulated C-peptide (SCP) measurements, serum leptin and clinical phenotype as follows: (i) Type 1A diabetes - AB+, (ii) Type 1B diabetes - AB- and FCP < 230 pmol/l and/or SCP < 660pmol/l, (iii) Type 2 diabetes - AB- and FCP > 500pmol/L and or SCP > 1160 pmol/l (iv) Untypeable diabetes - AB- and FCP 230-500 pmol/l and or SCP 660-1160 pmol/l and (v) Lipoatrophic diabetes - clinical phenotype and serum leptin. RESULTS: Fifty-eight participants (21M, 37F, age 20 ± 8 years, duration of diabetes 2.6 ± 2 years) were enrolled in the study. Using the classification criteria, Type 1 diabetes was the most common form of diabetes: 18(31%) Type 1A, 18(31%) Type 1B. Overall 22% (13 patients) had T2D. Patients with T2D were more likely to be female, older at diagnosis, obese and have a higher blood pressure when compared to those with Type 1 diabetes. In logistic regression analysis, age of diabetes onset, gender, BMI, systolic and diastolic blood pressure were significantly associated with T2D. Obesity measured by BMI was the strongest predictor of T2D. CONCLUSIONS: While Type 1 diabetes was the predominant form of diabetes in this study, a significant proportion of Jamaicans with youth onset diabetes may have T2D. Obesity is the strongest clinical predictor of Type 2 diabetes in the young diabetic patient.

OBJETIVOS: Evaluar la frecuencia de la aparición de la diabetes mellitus tipo 2 (DT2) en los jóvenes de (T2D) en Jamaica y las características de los jóvenes con esta forma de diabetes. MÉTODOS: Pacientes de dos importantes hospitales de remisión, fueron evaluados y diagnosticados con diabetes antes de los 25 años de edad y < 6 años antes del estudio. La clasificación se basó en la presencia de auto-anticuerpos (AC) GAD-65 e IA-2 de la diabetes, mediciones de péptido C en ayunas (PCA) y péptido C estimulado (PCE), leptina sérica y fenotipo clínico como sigue: (i) diabetes tipo A1 - AB+; diabetes tipo B1 - AB- y PCA < 230 pmol/l y/o PCE < 660 pmol/l; (iii) diabetes tipo 2 - AB - y PCA> 500pmol/L y/o PCE > 1160pmol/l; (iv) diabetes no tipificable - AB - y PCA 230-500 pmol/l y/o PCE 660-1160pmol/l; y (v) diabetes lipoatrófica - fenotipo clínico y leptina sérica. RESULTADOS: Cincuenta y ocho participantes (21 V, 37 H, 20 ± 8 años de edad, duración de la diabetes 2.6 ± 2 años) fueron enrolados en el estudio. Usando los criterios criterio de clasificación, la diabetes de tipo 1 fue la forma más común de diabetes: 18 (31%) tipo A1; 18 (31%) Tipo B1. En conjunto 22% (13 pacientes) tenían DT2. Los pacientes con DT2 presentaban una mayor probabilidad de ser mujeres, tener más edad a la hora del diagnóstico, ser obesos y tener una tensión arterial más alta en comparación con los que presentaban diabetes tipo 1. En el análisis de regresión logística, la edad de la aparición de la diabetes, el género, el IMC, la tensión arterial diastólica y sistólica estaban significativamente asociados con la DT2. La obesidad medida por el IMC fue el predictor más fuerte de la DT2. CONCLUSIONES: Aunque la diabetes tipo 1 fue la forma predominante de diabetes en este estudio, un número significativo de jamaicanos en los que la diabetes aparece en edad juvenil, pueden tener DT2. La obesidad es el predictor clínico más fuerte de la diabetes tipo 2 en el paciente diabético joven.

Dosagem do peptídeo C sérico ao acaso em adultos com diagnóstico clínico de diabetes mellitus tipo 1 / Random C peptide measurement in adults with clinical diagnosis of type 1 diabetes

OBJETIVO: A dosagem de peptídeo C (PC) pode ser útil para a classificação do Diabetes mellitus (DM). O objetivo deste estudo foi investigar a associação entre o diagnóstico clínico de DM tipo 1 e os níveis séricos de PC randômico. MÉTODOS: Foi feita dosagem de PC ao acaso em pacientes de origem multiétnica com diagnóstico clínico de DM tipo 1 na idade adulta ( > 18 anos). RESULTADOS: Estudamos 51 pacientes, sendo 28 mulheres (54,9 por cento) e 23 homens (45,1 por cento), 36 brancos (70,6 por cento) e 15 não-brancos (29,4 por cento) com idade média ao diagnóstico de 27,9 (±7,5) anos e duração média da doença de 9,9 (±7,2) anos. Oito pacientes (15,7 por cento) apresentaram PC > 1,5 ng/ml indicativo de função pancreática preservada. Neste grupo, foi detectado índice de massa corporal mais elevado (26,05 vs 23,05 kg/m²; p=0,006) e maior proporção de não-brancos (62,5 por cento vs 23,3 por cento; p=0,039) do que naqueles com PC baixo. CONCLUSÃO: A maioria dos pacientes com diagnóstico clínico de DM tipo 1 apresenta PC baixo. Entretanto, a secreção pancreática de insulina parece preservada em uma quantidade significativa de pacientes com quadro clínico indicativo de DM tipo 1. É possível que estes pacientes apresentem alguma forma atípica de DM, ainda não completamente compreendida, com características de DM tipo 1 e tipo 2 superpostas.

OBJECTIVE: C peptide measurement can be helpful for classification of diabetes mellitus (DM). The aim of this study was to investigate the association between clinical diagnosis of type 1 diabetes (T1D) and levels of random C peptide. METHODS: Random C peptide was measured in adults of multi-ethnic background who had been classified as having T1D according to their clinical presentation. All individuals were > 18 years old at onset. RESULTS: The study included 51 adults, 28 (54.9 percent) females and 23 (45.1 percent) males, 36 (70.6 percent) Caucasian and 15 (29.4 percent) non-Caucasian. Their mean age at onset and duration of DM mean age were 27.9 (± 7.5) years and 9.9 (±7.2) years, respectively. In 8 patients (15.7 percent) C peptide was > 1.5 ng/ml, indicating sustained beta cell function. In this group a higher level of body mass index (26.05 vs 23.05 kg/m²; p=0.006) and a greater proportion of non Caucasian individuals (62.5 percent vs 23.3 percent; p=0.039)) were detected. CONCLUSION: Most patients with DM clinically classified as T1D exhibit low C peptide. However, pancreatic insulin secretion seems to be preserved in a significant proportion of those individuals, possibly representing an atypical form of DM, not yet elucidated, that combines characteristics of both T1D and T2D.

Heterogeneidade do diabetes melito tipo 1 / Heterogeneity of type 1 diabetes mellitus

O diabetes melito tipo 1 (DM1) caracteriza-se pela deficiência de insulina por causa da destruição das células-beta pancreáticas. O DM1 atualmente é classificado em dois subtipos: um auto-imune (DM1A) e outro não auto-imune (DM1B). O DM1A poligênico (isolado ou associado a outras doenças auto-imunes) é a forma mais prevalente. O DM1A pode fazer parte de síndromes raras em virtude de alterações monogênicas [gene regulador da auto-imunidade (AIRE)] e mutações no gene FOX-p3. O DM1B corresponde de 4 por cento a 7 por cento do DM1 e pode incluir formas não clássicas, como o diabetes fulminante e o DATC. Jovens com DM1A e sinais de resistência à insulina associados têm sido denominados de diabetes duplo (DD), tipo 1 e tipo 2. Nessa revisão são discutidas as patofisiologias e as características clínicas das formas raras de DM1A, o DM1B, as formas atípicas de DM1 não auto-imune e as inter-relações entre a inflamação subclínica da obesidade e o processo auto-imune do DM1A no DD. Em resumo, apresentamos o conceito de heterogeneidade do DM1.

Type 1 diabetes (T1D) comprises all forms of autoimmune-mediated and idiopathic beta-cell destruction leading to absolute insulin deficiency. The etiological heterogeneity of T1D has been recognized for the last decades, but it has been divided into only two subtypes so far: autoimmune (T1D)A and non-autoimmune (T1D)B mediated. Polygenic T1DA (isolated or associated to other autoimmune diseases) is the most prevalent type of T1D. T1DA might be part of rare monogenic syndromes related to mutations in the autoimmune regulator gene (AIRE) and FOXp3. Non-autoimmune forms of T1D correspond to approximately 4 to 7 percent of newly diagnosed T1D and include T1DB, as well as other types of atypical diabetes, for example fulminant type 1 diabetes and adult ketosis-prone diabetes. A new expression of diabetes in young with insulin resistance and obesity, along with the presence of pancreatic autoimmunity markers, namely auto-antibodies to islet cell antigens, is called double diabetes (DD), T1DA plus type 2 diabetes. Evidence has been collected concerning the potential effect of obesity-linked cytokines in amplifying the autoimmune response in DD. Therefore all these issues are presented and discussed in this review as the concept of heterogeneity of Type 1 Diabetes.

The role of C-peptide in the classification of diabetes mellitus

We investigated twenty-one insulin-using patients, who had all been labelled as having diabetes mellitus (IDDM) or type one diabetes. Physicians have been erroneously using the term IDDM loosely to include all diabetics on insulin. The clinical criteria of the National Diabetes Data Group/WHO were used to reclassify these patients. Only thirteen were found to have IDDM and eight non-insulin dependent diabetes mellitus (NIDDM). Using fasting C-peptide values, only five of the thirteen with clinical IDDM truly had IDDM, the others might have maturity onset diabetes of the young (MODY) or diabetes in the young. Of the eight with clinical NIDDM seven had normal to high C-peptide values; the lone patient with low C-peptide values had diabetes diagnosed at 64 years. We conclude that the clinical classification of diabetes mellitus may be inaccurate and that C-peptide evaluation improves the accuracy of the classification.

Diabetes mellitus insulino dependiente (tipo I): actualización sobre su etiopatogenia / Type I insulin dependent diabetes mellitus: etiopathogenic update

La diabetes mellitus es una enfermedad poco frecuente en pediatría, cuyo diagnóstico debe sospecharse frente a un paciente con compromiso del estado general, poliuria y polidipsia y frente a todo paciente que ingresa en coma de causa no precisada. En los últimos años los avances en los estudios inmunológicos, genéticos y epidemiológicos han determinado que la destrucción de las células de los islotes de Langerhans, responsable de la diabetes infantil, es un proceso inmunológico regulado por una susceptibilidad genética. En este artículo se describe una actualización en los conocimientos de la etiopatogenia de la diabetes insulinodependiente o tipo I

Prevalencia del síndrome de Sjögren en diabetes mellitus / Prevalence of Sjögren's syndrome in diabetes mellitus

El objetivo del presente estudio fue conocer si el síndrome de Sjögren presenta una mayor prevalencia en los pacientes con diabetes mellitus que la población general. Se realizó un estudio prospectivo, ciego simple, comparativo en 50 pacientes con diabetes mellitus tipo I, 50 pacientes con diabetes mellitus tipo II y 50 sujetos control a los que se le diagnosticó síndrome de Sjögren definitivo o probable en base a criterios universalmente aceptados. Los pacientes con síndrome de Sjögren definitivo y probable en el grupo con diabetes mellitos tipo I fueron cinco, en el tipo II y en los controles dos sujetos, sin existir diferencia estadísticamente significativa entre ellos (x2=1.53, p=NS). Se puede concluir que la prevalencia del síndrome de Sjögren en los pacientes con diabetes mellitus no es mayor que en la población general

Diabetes mellitus en el anciano: enfermedad heterogénea, de clasificación dinámica y tratamiento predecible / Diabetes mellitus in elderly: a heterogeneous disease, of dinamic classification and predictable treatment

Para estudiar la presentación clínica y criterios de clasificación de la diabetes mellitus tipo I (DMI) en el anciano diabético (AD), se investigaron 258 pacientes diabéticos con más de 60 años, de los cuales 40 por ciento usaba insulina por haber fracasado el uso de hipoglicemiantes orales (HO). La prevalencia de cardiopatía isquémica fue 36 por ciento, enfermedad vascular periférica 34 por ciento y accidentes cerebro vasculares 30 por ciento; un 47 por ciento presentó retinopatía no-proliferativa, 37 por ciento neuropatía periférica simétrica y 16 por ciento nefropatía con una duración promedio de diabetes de 20 años. El 36 por ciento fueron obesos (IMC>25), 33 por ciento tuvieron hipertensión arterial y 12 por ciento dislipidemia. Péptido-C basal y post glucagon, antígenos HLA-DR y anticuerpos anti islote pancreático (ICA), fueron medidos en 75 AD en tratamiento, de los cuales 24 usaban insulina, 40 HO y 11 sólo dieta. Los AD en insulina, tuvieron un largo período de enfermedad, menos obesidad, niveles basales disminuídos de Péptido-C y baja respuesta de Péptido-C post glucagon (0.94 +/- 0.5 pmol/ml), en comparación con los tratados sólo con dieta (1.8 +/- 0.9 pmol/ml) y en HO (1.8 +/- 0.8 pmol/ml). Los ancianos diabéticos en insulino terapia tuvieron una mayor frecuencia de Ag HLA-DR3 (42 por ciento) y Ag HLA-DR4 (21 por ciento). Los ICA fueron negativos excepto en 2 pacientes. El presente estudio demuestra la alta prevalencia de enfermedad macrovascular y microvascular en los pacientes ancianos con diabetes mellitus y que el parámetro más confiable para caracterizar la insulinodependencia en éste grupo de edad, es la medición del Péptido-C basal y post glucagon. Los marcadores inmunogenéticos Ag HLA-DR e ICA, pueden ser utilizados concomitantemente, para ayudar a clasificar DMI en el anciano é instaurar un tratamiento insulínico racional

Diabetes mellitus: a study utilizing the revised diagnostic criteria

A group of 167 patients with various degree of glucose inlerance or at high risk of developing glucose intolerance were followed for five years at the Caguas Family Practice Center. Patients were classified using the criteria proposed by the National Diabetes Data Group and were monitored for the development of: a) diabetic complications, b) fasting glycemic control, c) changes in classification. There were 8 patients with IDDM, 55 patients with NIDDM and 104 patients in the high risk group. Only 6.2% of the high risk group developed complications while 87.5% of the IDDM and 67% of the NIDDM groups developed complications The most common overall complication was coronary artery disease. Three patients died of myocardial infarction during the study and nine patients changed classification. Two high risk patients developed overt diabetes, four shifted within the diabetic group, two within the high risk group and one diabetic regained a normal glucose tolerance