[Non classical subtypes of diabetes mellitus]. / Subtipos "no clásicos" de diabetes mellitus.

BACKGROUND: Some adult, obese and diabetic patients, initiate their disease with a severe diabetic ketoacidosis without a precipitating factor and do not require insulin thereafter. These patients are classified as having a "non classical" diabetes mellitus. AIM: To study the clinical, immunological, genetic and metabolic features of patients with non classical diabetes mellitus. PATIENTS AND METHODS: Ten patients (9 men, aged 45 +/- 12 years old) with non classical diabetes mellitus were studied. Anti islet and anti glutamic acid decarboxylase antibodies (ICA and anti GAD), HLA DQ alpha arginine 52 and non aspartic beta 57 were measured. Insulin secretion was measured by C peptide after glucagon injection and with the minimal model of Bergman. The latter model was also used to determine insulin sensitivity. RESULTS: Three patients were immunologically classified as type 1, since they had positive ICA or antiGAD antibodies and type 1 genetics (neutral or susceptible HLA DQ alpha and beta). They had insulin secretion after glucagon stimulus (C peptide ranging from 2.2 to 7.5 pmol/ml), but an almost absent response to a glucose load. They were also insulin resistant (a sensitivity index ranging from 0.05 to 1.67 x 10(-4) min/microU x ml). These three cases could be categorized as latent type 1. The other seven patients were ICA negative and antiGAD negative. Five had a susceptible HLA genotype for type 1 diabetes and two were neutral. All had insulin secretion after glucagon stimulation and a variable response to glucose. Six were insulin resistant (sensitivity index ranging from 0.32 to 1.29 x 10(-4) min/microU x ml). One patient was insulin sensitive (sensitivity index of 3.83 x 10(-4) min/microU x ml). Therefore all these patients were classified as type two diabetics with an atypical debut. CONCLUSIONS: Not all diabetics presenting with a severe diabetic ketoacidosis are type I. Among these, there are subjects with a latent type 1 diabetes or with an atypical type 2 diabetes.

[Glucotoxicity and lipotoxicity: factors in the pathogenesis and evolution of type 2 diabetes]. / Glucotoxicidad y lipotoxicidad: factores en la patogénesis y evolución de la diabetes tipo 2.

Glucose toxicity refers to the structural and functional damage in the beta cells and target tissues of insulin, caused by chronic hyperglycemia. These alterations cause a lower hormonal secretion and action (insulin resistance). Lipid toxicity refers to the damage caused by persistently high free fatty acid levels, as a consequence of triacylglycerol catabolism. Since elevated glucose and lipid levels cause a similar damage and interact, the term glucose and lipid toxicity refers to their additive effects. This toxicity can be implicated in the pathogenesis of type II diabetes and in the secondary failure of oral hypoglycemic drugs, leading to the requirement of insulin treatment. Insulin resistance with normal glucose levels, glucose intolerance and clinical diabetes are the three recognized stages in the development of type 2 diabetes. Considering that the first two stages are reversible, a good metabolic control to avoid glucose and lipid toxicity could revert or avoid the development of clinical diabetes.

[Evaluation of retinal involvement in type 2 diabetics with microalbuminuria]. / Evaluación del compromiso retinal en diabéticos tipo 2 microalbuminúricos.

BACKGROUND: In patients with type 2 diabetes, the presence of microalbuminuria, reflecting a widespread vascular damage, can be a marker of nephropathy, retinophaty and cardiovascular diseases. AIM: To study the relationship between microalbuminuria and the frequency, severity and outcome of retinopathy in patients with type 2 diabetes mellitus. PATIENTS AND METHODS: One hundred patients with type 2 diabetes were subjected to a clinical examination, serial monitoring of blood pressure and quarterly measurement of microalbuminuria by RIA. Annually, a fundoscopy, a color photography of the posterior pole and retinal angiofluorescence were performed. Retinopathy was classified as basal (mild to moderate), preproliferative and proliferative. Sixty-four normoalbuminuric patients (urinary albumin of less than 30 mg/24 h) were included in group 1 and 36 patients with a urinary albumin over 30 mg/24 h in group 2. Fifty seven patients with normal blood pressure were randomly treated with enalapril or placebo and those with hypertension received enalapril or acebutolol to normalize blood pressure. RESULTS: Sixty one percent of group 1 patients and 41% of group 2 patients has retinopathy (p < 0.05). The retinal lesions were proliferative in 41% of group 2 patients and in 8% of group 1 patient (p < 0.05). Retinopathy was present in 67% of hypertensive patients of group 2 and in 41% of hypertensive patients of group 1. An unfavorable evolution of retinopathy was observed in 22% of group 2 patients and in 5% of group 1 patient (p < 0.05). CONCLUSIONS: In type 2 diabetic patients, the presence of microalbuminuria is a prediction of a higher frequency, severity and dismal evolution of diabetic retinopathy (Rev Méd Chile 2000; 128: 1085-92).

[Decompensated diabetes mellitus and hyperchloremic metabolic acidosis: a case with both pathologies]. / Diabetes mellitus descompensada y acidosis metabólica hiperclorémica: asociación de patologías en un caso.

Diabetic ketoacidosis is manifested by elevated blood glucose levels, ketosis and metabolic acidosis with increased anion gap. A transitory hyperchloremic acidosis, with normal anion gap, can appear. We report a 21 years old female with a type 2 diabetes mellitus, admitted to the emergency room of a general hospital with hyperglycemia, absence of ketonemia, severe hypokalemia and hyperchloremic metabolic acidosis. Initially, she was diagnosed and treated as a severe diabetic ketoacidosis. Normal blood glucose levels were rapidly achieved but electrolyte and acid base alterations persisted, leading to the suspicion that another associated condition was causing the acidosis and hypokalemia. Urinary pH and anion gap measurement, the study of renal acidification and a bicarbonate overload test lead to the diagnosis of a distal renal tubular acidosis, secondary to a Sjögren syndrome, that was confirmed with a Schirmer test and positive anti Ro antibodies. In this diabetic patient, the acute hyperglycemia intensified the hypokalemia of her distal renal tubular acidosis and unchained the acute metabolic condition.

[Microalbuminuria, lipid changes and coronary heart disease in non-insulin-dependent diabetics]. / Microalbuminuria, alteraciones lipídicas y cardiopatía coronaria en diabéticos no insulino dependientes.

BACKGROUND: Microalbuminuria could be a possible coronary risk factor: AIM: To study the association between microalbuminuria, serum lipid levels and coronary heart disease in non-insulin-dependent diabetics. PATIENTS AND METHODS: We studied 104 non-insulin-dependent diabetics, who were separated in four groups according to the presence of microalbuminuria, defined as a 24 h albumin excretion of 30-300 mg/24 h and according the history of coronary artery disease. Total, HDL and LDL cholesterol, triglycerides, alpha, beta, prebeta lipoproteins, lipoprotein (a), apoproteins A and B were measured in all. RESULTS: Twenty patients with and 32 without coronary artery disease had normal albumin excretion and the same number of patients had a urinary albumin 30-300 mg/24 h. All four groups were comparable in terms of metabolic control, nutritional status, blood pressure and creatinine levels. Patients with coronary artery disease had higher urinary albumin excretion than patients without the disease 91 (32-173) and 34 (5-97) mg/24 h respectively p < 0.01. Patients with coronary artery disease and microalbuminuria had higher triglycerides, beta, pre beta lipoproteins, Apo B, Lp(a) and lower Apo B and alpha lipoproteins. This group also had a higher frequency of abnormal pre beta and alpha lipoprotein levels, when compared with coronary patients with normal albumin excretion. In coronary patients there was a positive association between urinary albumin levels and triglycerides (r = 0.24), pre beta lipoproteins (r = 0.27) and Apo B (r = 0.3); there was also a negative association with HDL cholesterol (r = 0.25) and alpha lipoproteins (r = -0.41). CONCLUSIONS: In this group of non-insulin-dependent diabetics, an association among microalbuminuria, abnormal serum lipid levels and coronary artery disease was detected.

[Clinical experience with an alpha glucosidase inhibitor (acarbose) in the treatment of non-insulin-dependent diabetes. Multicenter study]. / Experiencia clínica con un inhibidor de la alfa glucosidasa (acarbosa) en el tratamiento de la diabetes no insulinodependiente. Estudio multicéntrico.

BACKGROUND: Acarbose, an alpha glucosidase inhibitor is a drug used in the treatment of non insulin dependent diabetes mellitus, that interferes with the intestinal absorption of monosaccharides. AIM: To study the effect of acarbose in non insulin dependent diabetic patients that had an inadequate metabolic control with diet and sulphonylureas. PATIENTS AND METHODS: Diabetic patients received acarbose, 150 mg/day during four weeks and this dose was increased to 300 mg/day during 3 months. Afterwards, patients were followed for a period of 12 weeks without acarbose. Fasting and post-prandial blood glucose and glycosilated hemoglobin were measured sequentially during the study. RESULTS: Eighty five patients were recruited for the study but 64 complied with the treatment protocol. The age of these patients was 56 +/- 8.8 years old, their diabetes duration was 7.8 +/- 8.8 years and their body mass index was 27.6 +/- 3.6 kg/m2. During acarbose treatment, glycosilated hemoglobin decreased from 8.36 +/- 1.33 to 7.71+ 1.7% (p < 0.001), fasting blood glucose decreased from 173 +/- 48 to 159 +/- 59 mg/dl (p < 0.03) and post-prandial blood glucose decreased from 254 +/- 80 to 241 +/- 80 mg/dl (NS). After discontinuing acarbose glycosilated hemoglobin and blood glucose levels returned to basal levels. Body weight and blood pressure did not change during the treatment period. Fifty nine patients had gastrointestinal symptoms (meteorism, flatulence and abdominal distention) that were mild in 59% and moderate in 39%. Episodes of hypoglycemia were not observed. CONCLUSIONS: Acarbose, associated to sulphonylureas is an effective drug to reduce blood glucose and glycosilated hemoglobin levels in patients with non insulin dependent diabetes.

One of the lowest validated incidence rates of insulin dependent diabetes mellitus in the Americas: Santiago, Chile.

The goal of this study was to estimate the average annual incidence rate of insulin-dependent diabetes mellitus (IDDM) in Santiago as part of a Multinational Project in Childhood Diabetes (Diabetes Mondiale or DiaMond). Incidence was calculated among subjects under 15 years of age, through a retrospective search and confirmation method from 1 January 1986 to 31 December 1992. Hospitals and private offices of endocrinologists and specialists in diabetes were surveyed. A total of 252 registered cases, 118 boys and 134 girls, for an annual incidences of 2.36/100,000 hab.year. which is one of the lowest validated rates in the Americas.

[Urinary albumin excretion in non-insulin-dependent diabetic patients. Effects of an angiotensin-converting enzyme inhibitor]. / Excreción urinaria de albúmina en diabéticos no insulino-dependientes. Efecto de un inhibidor de la enzima convertidora de angiotensina.

BACKGROUND: Microalbuminuria in diabetic patients is diagnostic of early renal involvement and angiotensin converting enzyme inhibitors reduce albumin excretion in these subjects. AIM: To assess the effects of an angiotensin converting enzyme inhibitor on urinary albumin excretion in non insulin dependent diabetic patients. PATIENTS AND METHODS: Diabetic patients with normal blood pressure were randomly assigned to receive enalapril 10 mg/day or placebo and followed during 18 months. Those with high blood pressure were randomly assigned to receive enalapril or acebutolol in doses necessary to normalize blood pressure and followed during 12 months. Every three months, urinary albumin excretion was measured in a four hour urine sample by radioimmunoassay. RESULTS: One hundred fifty two patients were recruited for the study and 46 were lost from follow up. In 17 subjects with normal blood pressure initial urinary albumin excretion below cutoff values (30 mg/24 h) and treated with enalapril, this parameter did not change; in 20 treated with placebo, it increased from 5.8 +/- 6.1 to 18.2 +/- 7.5 mg/24 h. In 11 patients with normal pressure and increased initial urinary albumin, this parameter did not change with enalapril and increased in 10 with placebo from 87.3 +/- 75.1 to 253.6 +/- 61.1 mg/24 h. In hypertensive patients with normal urinary albumin excretion, no changes in this parameter were observed in those treated with acebutolol (n = 10) or enalapril (n = 14). In hypertensives with high urinary albumin excretion, it decreased from 119.2 +/- 8.5 to 40.0 +/- 4.7 mg/24 h with enalapril treatment (n = 12), and no change was observed in those treated with acebutolol (n = 11). CONCLUSIONS: Enalapril decreases urinary albumin excretion in non insulin dependent diabetic patients.

[Incidence of insulin-dependent diabetes mellitus in Santiago, Chile (1990-1993)]. / Incidencia de diabetes mellitus insulino dependiente en santiago, Chile (1990-1993).

The aim of this study was to determine IDDM incidence in the Metropolitan Region of Chile, during the period 1990-1993 as part of the Multinational Project for Childhood Diabetes (WHO DIAMOND Project Group). The studied population was 1499.784 inhabitants. All children in whom the diagnosis was made between January 1, 1990 and December 31, 1993 were included. We used a retrospective and prospective search and confirmation method, using as data sources public and private hospitals and medical records of Pediatricians. The Juvenile Diabetes Foundation was used as a secondary data source. All cases had at least two confirmation sources. A total of 176 new cases (90 male) were diagnosed in the study period, with an annual incidence of 2.92/100,000 for females and 2.95 for males. The group of children from 10 to 14 years old had the highest incidence rate (4.9/100,000), specially in women (5.25/100,000). The yearly incidence was 1.31 in 1990, 2.71 in 1991, 2.93 in 1992 and 3.7/1000,000 in 1993. It is concluded that the Metropolitan Region has one of the lowest incidences of IDDM in Latin America, although it increased along the study years.

[Genetic predisposition to develop insulin-dependent diabetes mellitus. A population study in Santiago and Temuco, Chile]. / Predisposición genética para desarrollar diabetes mellitus insulino-dependiente. Estudio en población de Santiago y Temuco, Chile.

Insulin-dependent diabetes mellitus (IDDM) is strongly associated with particular HLA-DQ alpha/beta markers in white population. The heterodimers conformation composed of a DQ alpha chain with an arginine at residue 52 (Arg52) combined to a DQ beta chain lacking an aspartic acid at residue 57 (non Asp57) increase markedly the risk to develop IDDM. To confirm this association, 63 IDDM patients from Santiago de Chile registry, 20 IDDM patients from Temuco registry and 74 unrelated healthy non diabetic control subjects were studied. With polymerase chain reaction (PCR) and sequence specific oligonucleotide probes the individuals were typed for their HLA-DQA1 and DQB1 alleles, their DQA1/DQB1 genotype and heterodimers conformation were compared. In diabetic population both markers Arg52 homocygote and non Asp57 homocygote were markedly increased regard to control subjects (R/R: 0.76 and 0.85 vs 0.33; ND/ND: 0.78 and 0.75 vs 0.50, p < 0.05). A high relative risk (RR) was determined for both homocygote markers in IDDM groups. Arg52 DQ alpha (R)/non Asp57 DQ beta (ND) heterodimers were strongly associated with susceptibility to IDDM. A high RR was observed in patients with four susceptibility DQ heterodimers (RR1: 13.7 in IDDM-Santiago and RR2: 18.6 in IDDM-Temuco, p < 0.00003). The HLA-DQ alpha/beta markers and their risk heterodimers are increased in our diabetic population and could be considered as susceptibility markers to develop IDDM.

[Reversibility of early stage diabetic nephropathy]. / Reversibilidad de la nefropatia diabetica en etapas precoces.

A double blind crossover trial was performed on the effect of enalapril on urinary albumin excretion (UAE) in normotensive insulin dependent diabetics. Nineteen normoalbuminuric (UAE < 30 mg/24 h) and 17 microalbuminuric patients (UAE > 30 and < 300 mg/4 h) were studied; all patients had post prandial blood glucose levels < 180 mg/dl, HbA1 < 11% and none had chronic diabetic complications. Both groups had similar age, years of diabetes, body mass index and protein ingestion (70 g/day). Fifty percent of patients in each group received 5 mg/day of enalapril or placebo during one year, and during the second year the therapy was switched. No changes were observed in blood pressure, post prandial blood glucose, HbA1 and plasma electrolytes during the study period. A reduction in creatinine clearance, within normal limits, in both groups of patients treated with enalapril and no modifications with placebo were observed. UAE decreased significantly in normo and microalbuminuric patients initially treated with enalapril from 19 +/- 8 to 8 +/- 2 and from 71 +/- 19 to 39 +/- 12 mg/24 h respectively. These values increased during the placebo period to 23 +/- 6 and 47 +/- 13 mg/24 h respectively. Among those initially treated with placebo, UAE increased only in normoalbuminurics from 19 +/- 7 to 28 +/- 9 mg/24 h. During subsequent treatment with enalapril, UAE decreased in both groups. It is concluded that, in this group of patients, enalapril decreases UAE, possibly preventing the progression to severe forms of diabetic nephropathy.

[Acipimox in primary hyperlipidemias: safety and efficacy evaluated in six months]. / Acipimox en hiperlipidemias primarias: seguridad y eficacia evaluada a 6 meses.

The efficacy and tolerance of 750 mg of Acipimox was tested in 38 pts with primary dyslipidemias: 20 type IIa, 12 type IIb, and 6 type IV. All pts had been poor responders to a 2 month diet according to the recommendations of the National Cholesterol Education Program. Clinical examination, eye fundus, and the following laboratory tests: total cholesterol (TC), HDL, triglycerides (TG), total bilirubin, alkaline phosphatase, oxalacetic and pyruvic transaminases, uric acid, plasmatic creatinine, albumin, postprandial glucose test, hematocrit, white blood and platelet count were performed 60 days before drug initiation, 60 and 180 days after treatment had been started. No side effects were observed (myositis, visual gastrointestinal). 50% of the pts had slight to moderate flushing which appeared the first 3 days and lasted 14 +/- 7 days after treatment had been started. Plasmatic creatinine increased from 0.89 to 1.86 mg/dl in pt with one kidney, returning to normal levels 30 days after Acipimox interruption. After 180 days of therapy in the IIa group TC was -27% (p < 0.001), HDL + 15% (p < 0.001); in the IIb group: TC-23% (p < 0.001), HDL +9% (NS), TG -48% (p < 0.001); and in the IV group: TC-10% (p < 0.05), HDL +20% (p < 0.001), TG-53% (p < 0.001). Acipimox is well tolerated and is useful as a lipid-lowering drug in type IIa, IIb and IV dyslipidemias. Further studies are necessary to clear effects of the drug on renal metabolism and on long term survival of coronary pts.

[Incidence of insulin-dependent diabetes mellitus in the metropolitan region]. / Incidencia de diabetes mellitus insulinodependiente en la región metropolitana.

We used a retrospective search and confirmation method to establish the number of new cases of insulin dependent diabetes mellitus diagnosed between Jan 1, 1986 and Dec 31, 1989 in subjects under 15 years of age in the Metropolitan region of Chile. All hospitals and outpatient facilities of the National Health Service, other hospitals and private offices of endocrinologists and specialists in diabetes were surveyed, as well as the registry from the Juvenile Diabetes Foundation. A total of 115 cases, 52 in males and 63 in females were found, for an annual incidence of 1.69 and 2.15 per 100,000, respectively. Overall, the annual incidence rates were 2.22 in 1986, 1.22 in 1987 (p < 0.001), 2.13 in 1988 and 2.09 in 1989. A greater number of cases was diagnosed at age 4 in males and at age 12 in females (p < 0.001). The greater number of cases were diagnosed from June to August (winter) and the lowest in October (p < 0.001).

Confiabilidad de los métodos semicuantitativos en la determinación de microalbumina / Reliability of semiquantitative methods for the determination of microalbuminuria

En los diabéticos la nefropatía se presenta con una mayor prevalencia que en la población general; la microalbuminuria (excreción urinaria de albúmina entre 20 y 200 mg/l) constituye un índice predictivo de su desarrollo y un elemento útil de detección precoz en etapas reversibles. En 50 diabéticos,se comparan los resultados de la determinación de microalbuminuria con radioinmunoanálisis (RIA) (método cuantitativo) y con tres procedimientos semicuantitativos; tabletas indicadoras, sistema látex-anticuerpo y tiras reactivas indicadoras.Los resultados obtenidos revelan alta concordancia de los métodos semicuantitativos con RIA. En consecuencia, los primeros son procedimientos confiables y de gran utilidad en la pesquisa de microalbuminuria y, por ende, de nefropatía diabética en etapas iniciales y reversibles

Confiabilidad de los métodos semicuantitativos en la determinación de microalbumina / Reliability of semiquantitative methods for the determination of microalbuminuria

En los diabéticos la nefropatía se presenta con una mayor prevalencia que en la población general; la microalbuminuria (excreción urinaria de albúmina entre 20 y 200 mg/l) constituye un índice predictivo de su desarrollo y un elemento útil de detección precoz en etapas reversibles. En 50 diabéticos,se comparan los resultados de la determinación de microalbuminuria con radioinmunoanálisis (RIA) (método cuantitativo) y con tres procedimientos semicuantitativos; tabletas indicadoras, sistema látex-anticuerpo y tiras reactivas indicadoras.Los resultados obtenidos revelan alta concordancia de los métodos semicuantitativos con RIA. En consecuencia, los primeros son procedimientos confiables y de gran utilidad en la pesquisa de microalbuminuria y, por ende, de nefropatía diabética en etapas iniciales y reversibles

[Microalbuminuria in insulin-dependent diabetics: the prevention of diabetic nephropathy]. / Microalbuminuria en diabéticos insulinodependientes: prevención de la nefropatía diabética.

We evaluated the effects of angiotensin converting enzyme inhibition upon the urinary excretion of albumin in 36 insulin dependent normotensive diabetic patients with adequate metabolic control and no evidence of renal failure. 19 subjects had normal levels of albumin excretion (< 30 mg/24 h) and 17 showed microalbuminuria from 30 to 300 mg/24 h. Half of the patients were randomly selected in each group to receive enalapril, 5 mg/day. A progressive decrease in albumin excretion levels was observed for both enalapril treated subgroups, from 18.9 +/- 8.3 to 8.1 +/- 2.7 mg/24 h (normoalbuminurics) and from 73.1 +/- 25.0 to 40.1 +/- 26.3 mg/24 h (microalbuminurics). In contrast, an increase in albumin excretion from 19.4 +/- 6.8 to 29.4 +/- 14.2 mg/24 h was observed in non treated normoalbuminuric patients. Untreated patients with microalbuminuria remained with stable albumin excretion levels (67.4 +/- 39 to 64.8 +/- 23.4 mg/24 h). Enalapril treatment was associated to a significant (p < 0.05) decrease in creatinine clearance which remained within normal limits. Blood pressure, Na and K plasma levels and total proteins remained normal throughout the study. Thus, angiotensin converting enzyme inhibition reduces the urinary excretion of albumin in insulin dependent diabetics with normo or microalbuminuria.