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Substrates of semicarbazide-sensitive amine oxidase (SSAO) exert insulin-like actions in adipocytes. One of them, benzylamine (Bza) exhibits antihyperglycemic properties in several rodent models of diabetes. To further study the antidiabetic potential of this naturally occurring amine, a model of severe type 2 diabetes, the obese db-/- mouse, was subjected to oral Bza administration. To this end, db-/- mice and their lean littermates were treated at 4 weeks of age by adding 0.5% Bza in drinking water for seven weeks. Body mass, fat content, blood glucose and urinary glucose output were followed while adipocyte insulin responsiveness and gene expression were checked at the end of supplementation, together with aorta nitrites. Bza supplementation delayed the appearance of hyperglycemia, abolished polydypsia and glycosuria in obese/diabetic mice without any detectable effect in lean control, except for a reduction in food intake observed in both genotypes. The improvement of glucose homeostasis was observed in db-/- mice at the expense of increased fat deposition, especially in the subcutaneous white adipose tissue (SCWAT), without sign of worsened inflammation or insulin responsiveness and with lowered circulating triglycerides and uric acid, while NO bioavailability was increased in aorta. The higher capacity of SSAO in oxidizing Bza in SCWAT, found in the obese mice, was unaltered by Bza supplementation and likely involved in the activation of glucose utilization by adipocytes. We propose that Bza oxidation in tissues, which produces hydrogen peroxide mainly in SCWAT, facilitates insulin-independent glucose utilization. Bza could be considered as a potential agent for dietary supplementation aiming at preventing diabetic complications.

Cluster analysis using age, BMI, glycemia and homeostasis model estimates (HOMA-IR, -B) revealed distinct risk profiles for progression of diabetic nephropathy in large cohorts, but its relevance for other diabetes-related comorbidities remains unclear. We aimed to (i) examine whether intensified phenotyping would confirm the results of this cluster analysis and (ii) test the hypothesis that liver fat content (HCL), as marker of nonalcoholic fatty liver disease (NAFLD), differs among clusters at diabetes diagnosis and during follow-up. Thus, this cluster analysis was applied to recent-onset patients with non-autoimmune diabetes of the German Diabetes Study. This identified 286 mild age-related (MARD, 44%), 268 mild obesity-related (MOD, 42%), 66 severe insulin-resistant (SIRD, 10%) and 27 severe insulin-deficient (SIDD, 4%) diabetes patients. Furthermore, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps, HCL by magnetic resonance spectroscopy and hepatic fibrosis by a noninvasive score (NAFLD-FS). Congruently, whole-body insulin sensitivity was lowest in SIRD compared to MOD, SIDD and MARD (4.3±2.0 vs. 5.6±2.4, 6.5±2.6, 7.6±2.8 mg*kg-¹*min-¹, all p0.6) was highest in SIRD (21%) compared to SIDD (0%), MOD (16%) and MARD (11%). In conclusion, patients of the SIRD cluster exhibit higher prevalence of steatosis at diagnosis and increased risk of NAFLD progression over 5 years. Disclosure O.P. Zaharia: None. K. Strassburger: None. Y. Kupriyanova: None. Y. Karusheva: None. S. Antoniou: None. K. Bodis: None. O. Asplund: Research Support; Self; Eli Lilly and Company. V. Burkart: None. K. Muessig: None. J. Hwang: None. O. Kuss: None. L. Groop: None. E. Ahlqvist: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc. Funding German Ministry of Culture and Science of the State of North Rhine-Westphalia; German Federal Ministry of Health; German Federal Ministry of Education and Research

Obesity is a state of metabolic dysregulation of the whole organism and a major contributing factor to the epidemic of insulin resistant diabetes. The non-pharmacological treatment of obesity with bariatric surgery results in a dramatic and almost instantaneous reversal of insulin resistance. The present review collectively addresses the evidence for this phenomenon in the literature and discusses potential metabolic and neurohumoral mechanisms. We propose that nutrient restriction lowers the cell’s defense mechanisms for nutrient overload in insulin responsive organs.

We report a diagnosis of diabetes type 2 suggested by diffuse omental infiltration seen on computed tomography which resolved following treatment. There have been reports of increased macrophage infiltration in the omental fat of diabetic patients which we believe is identifiable by CT. To our knowledge, the diagnosis of diabetes with CT has not yet been reported. Diabetes type 2 is commonly a clinical diagnosis. However, undiagnosed diabetic patients may present with nonspecific manifestations and CT may be ordered as part of the initial evaluation. We present a case in which diabetes type 2 was suggested by diffuse omental infiltration.

Rationale: Alström syndrome is an autosomal recessive disorder characterized by hearing loss, blindness, obesity, non-insulin dependent diabetes, and others. Patient concern: A 10 years old Saudi girl, who presented with diabetic ketoacidosis and found to have hearing loss and blindness. Diagnosis: Alström syndrome. Interventions: Multidisciplinary team approach, with echocardiography, hearing test, eye exam and genetic test for Alström syndrome. Outcomes: The patient has retinitis pigmentosa, bilateral hearing loss, double diabetes with weakly positive anti-insulin antibodies and DNA analysis showed novel mutation for Alström syndrome. Lessons: the combination of obesity, diabetes, hearing loss and blindness should alert the physician to test for Alström syndrome.

espanolIntroduccion: El Sindrome de Alstrom es una enfermedad autosomica recesiva. Se conoce un gen (ALMS1) asociado al sindrome, caracterizado por ceguera causada por distrofia de conos y bastones, sordera sensorial, resistencia a la insulina, obesidad, y cardiopatias. Caso clinico: Nino de cuatro anos que tras una parada cardiorrespiratoria es diagnosticado de cardiomiopatia dilatada. Comienza con nistagmus y fotofobia. Se le realiza exploracion oftalmologica y ERG, siendo los resultados compatibles con un Sindrome de Alstrom. Discusion: El diagnostico en estos casos es clinico. El diagnostico de certeza con tecnicas moleculares es posible en un 25-40% de casos. El tratamiento es sintomatico. EnglishIntroduction: Alstrom-Hallgren syndrome is an inherited condition in which the transmission of a double dose of a mutated gene leads to specific clinical findings. To the present time there has been only one gene detected which leads to this syndrome, the ALMS1 gene. Mutation of this gene leads to progressive blindness due to photoreceptor dystrophy, progressive sensorineural hearing loss, insulin resistant diabetes, morbid obesity and cardiologic abnormalities. Clinical Case: We present the case of a four-year-old male who, after a cardiopulmonary shutdown in the fourth month of life, was diagnosed with a dilated cardiomyopathy. Nystagmus and photophobia followed, and, after ophthalmologic exploration and an electroretinogram, the results were consistent with Alstrom syndrome. The appropriate genetic studies were then performed. Discussion: The diagnosis in this case was considered basically because of its uncommon clinical features, and the fact a multidisciplinary approach was used in its evaluation. We were only able to confirm the diagnosis by molecular biology techniques, with this resulting in the correct diagnosis in 25-40% of cases. Treatment is symptomatic and the prognosis extremely variable.

LONG-TERM TREATMENT WITH RECOMBINANT HUMAN INSULIN-LIKE GROWTH FACTOR- 1 (rhlGF)FOR PATIENTS WITH EXTREME INSULIN RESISTANT DIABETES

A family is presented in which at least five members in three generations suffered a characteristic syndrome of generalised lipoatrophy, sparing the head and neck, and muscle hypertrophy variably associated with high plasma insulin and lipid levels and insulin resistant diabetes. This pedigree contains the first documented affected male with the syndrome. The diagnosis is of practical importance since close medical supervision of asymptomatic gene carriers is likely to improve their prognosis. The findings in this family have relevance also to the study of insulin and lipid metabolism.

Premature eruption and macrodontia associated with insulin resistant diabetes and pineal hyperplasia. Report of two cases

We describe three siblings with a mild diabetes mellitus in combination with acanthosis nigricans and multiple minor physical abnormalities. Fasting plasma insulin was elevated up to 100-fold as compared with normal values, and the diabetes was classified as insulin resistant. Insulin-binding studies on erythrocytes, monocytes, and cultured fibroblasts disclosed an abnormally reduced binding capacity, as compared with that of healthy controls, which was most prominent at low concentrations of insulin. Scatchard analysis on erythrocytes of the three patients revealed a normal number of total insulin-binding sites per cell, but a complete lack of insulin binding to the high-affinity receptor component. The findings are consistent with the assumption of two genetically distinct types of insulin receptors.

1. A patient with insulin resistant diabetes mellitus has been described in detail with emphasis upon the time relationship between prior insulin therapy for mental illness and the subsequent development of overt diabetes. 2. The localization of the insulin antibodies in the γg-globulins with some extension into the region of γa has been delineated. 3. The possible relationship between the immunologic responsiveness of the patient and the eventual manifestation of the disease is discussed.

IT IS WELL known that certain adrenal cortex hormones have a profound effect on carbohydrate metabolism. Ingle 1 has induced frank diabetes in normal rats with daily doses of 5 to 10 mg. of cortisone. Sprague and his associates 2 have contrasted the action of cortisone in subjects who had Addison's disease alone with its effect on patients who had coexisting diabetes and Addison's disease. In the former cortisone abolished the tendency toward development of hypoglycemia; in the latter cortisone greatly increased dextrose excretion. In nondiabetic subjects cortisone produced abnormal dextrose tolerance curves. 2 The following case history is reported because the administration of nitrogen mustard (methyl- bis [beta-chloroethyl] amine hydrochloride) reversed an insulinresistant diabetes which developed when cortisone was given to a diabetic patient. REPORT OF CASE M. Z., a 53 year old white married man, was first admitted to Memorial Hospital on March 16, 1950, with a diagnosis

EXTENSIVE clinical and experimental research has been carried out with the new hypoglycemic sulfonylureas to elucidate the mode and site of their action, which up to now has not been conclusively established. Although it is generally agreed that these drugs may be substituted, on the average, for about 20 to 40 units of insulin, I have been able, with the help of tolbutamide,‡ to reduce the daily insulin requirement of a patient with insulin-resistant diabetes on one occasion from 2000 units to 450 units and on another occasion from 900 units to 200 units — that is, to about 25 . . .

CONTRARY to speculation diabetes mellitus that follows total pancreatectomy in man is relatively mild. In the absence of infection or other complications the requirement for insulin is usually stable and ranges from 20 to 40 units daily. There is relatively little tendency to spontaneous ketosis and coma, but insulin sensitivity has been a frequent problem in management. The marked contrast of these findings with those in many cases of naturally occurring diabetes mellitus has stimulated consideration of factors besides lack of insulin that produce hyperglycemia and ketosis and require large doses of insulin for correction. In the following case, which . . .