Comparison of insulin lispro protamine suspension and insulin detemir in basal-bolus therapy in patients with Type 1 diabetes.

AIMS: The efficacy of two basal insulins, insulin lispro protamine suspension (ILPS) and insulin detemir, was compared in basal-bolus regimens in Type 1 diabetes. METHODS: In this 32-week, multinational, parallel-group, randomized, controlled trial, adult patients with Type 1 diabetes received ILPS or insulin detemir, injected twice daily (before breakfast and bedtime) and prandial insulin lispro three times daily. The primary outcome was change in glycated haemoglobin (HbA(1c)) from baseline to endpoint. RESULTS: Least squares mean (+/-se) changes in HbA(1c) were similar between groups, meeting non-inferiority (margin, 0.4%): -0.69 +/- 0.07% for ILPS and -0.59 +/- 0.07% for insulin detemir [between-treatment difference -0.10%; 95% confidence interval (CI) -0.29, 0.10]. Standard deviation of fasting blood glucose was similar (non-inferiority margin 0.8 mmol/l): 2.74 +/- 0.14 mmol/l for ILPS and 2.38 +/- 0.14 mmol/l for insulin detemir (CI -0.03, 0.75). Patients on ILPS gained more weight (1.59 +/- 0.23 kg vs. 0.62 +/- 0.24 kg; CI 0.34, 1.60; margin 1.5 kg). Weight-adjusted daily total and prandial insulin doses were lower for ILPS (prandial insulin, 0.38 +/- 0.01 U/kg/day for ILPS, 0.44 +/- 0.01 U/kg/day for insulin detemir; P = 0.004); daily basal insulin dose was similar. All hypoglycaemia incidence and rate and nocturnal hypoglycaemia incidence were similar between groups; nocturnal hypoglycaemia rate was lower for insulin detemir (mean +/- sd 0.79 +/- 1.23 for ILPS, 0.49 +/- 0.85 for insulin detemir; P = 0.001). Severe hypoglycaemia rate was 0.03 +/- 0.11 for ILPS and 0.02 +/- 0.10 for insulin detemir (P = 0.37). CONCLUSIONS: ILPS-treated patients with Type 1 diabetes achieved similar glycaemic control as insulin detemir-treated patients after 32 weeks. Glucose variability was similar. While weight gain and nocturnal hypoglycaemia rate were statistically higher with ILPS, the clinical relevance is unclear.

Predicted annual costs for inpatients with diabetes and foot ulcers in a developing country-a simulation of the current situation in Brazil.

AIMS: The objective of this cost-of-illness analysis was to quantify the annual costs associated with hospital admission for people with diabetes and foot ulcers in Brazil. METHODS: A hypothetical cohort was simulated using a decision tree model. Prevalence and incidence rates and clinical outcomes were estimated from published studies and applied to the general Brazilian population over 30 years. Costs were quoted in Brazilian real (BRL) and converted to US dollars ($US) at the 2008 currency exchange rate ($US1 = BRL 1.64). In the sensitivity analysis, we reduced and increased rates to assess the robustness of the cost estimates. RESULTS: In this hypothetical cohort there are 6.48 million (95% confidence interval 4.47-7.12) Brazilians citizens with Type 2 diabetes. Each year, approximately 323,000 (89,500-484,500) of these people develop foot ulcers and almost 97,200 (17,900-169,600) require hospital admission as a result. Each year, almost 46,300 (8500-80,900) limb amputations and 12,400 (2300-21,700) deaths occur as a result of diabetic foot disease in Brazil. The annual cost associated with these hospital admissions is estimated to be almost $US264m ($US51m-461m). The estimated cost for patients with amputation is nearly $US128m ($US24.5m-222.3m). CONCLUSIONS: Our model shows that the social and economic impact of diabetic foot disease in Brazil is high. Government decision makers should reflect on the current situation and provide organized foot care throughout the whole country.

Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial.

AIMS: Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy. METHODS AND PATIENTS: A total of 768 patients (18-77 years; HbA(1c) screening >or= 7.5 to

Influence of antecedent carbohydrate intake on the biphasic insulin response to intravenous glucose.

The insulin secretory response to a sudden and sustained intravenous glycemic stimulus was measured in three groups of dogs whose antecedent carbohydrate intake ranged from zero to 300 or more grams daily. Insulin outflow rate from the pancreaticoduodenal vein was measured every minute for ten minutes, then at increasing intervals through sixty minutes. It was found that starvation erased the first phase of the biphasic insulin response shown by dogs on ordinary carbohydrate intake and that high-carbohydrate intake abolished the trough between the two phases. The data suggest that, during truly physiologic stimulation of insulin secretion, the latter represents the final stage of a continuum of hormonal synthesis, storage, and release, rather than emanating from one of two separate pools of fast-versus-slow insulin secretion.

Uniphasic insulin-secretory response in the pancreatic vein of dogs after an enteric glucose load.

The insulin secretory response to an enteric glucose load was measured in 11 dogs after intrajejunal instillation of a 25 per cent glucose solution (1.75 gm./kg.) in five minutes. Insulin outflow rate was measured every minute for 10 minutes, then at increasing intervals through 60 minutes. Starting at two minutes after onset of glucose loading, mean arterial plasma glucose rose steadily throughout the hour. This was paralleled by a similarly progressive rise in mean pancreatic venous plasma insulin output starting at seven minutes and peaking at 50 minutes, despite partial masking by a simultaneous fall in pancreatic venous plasma flow rate after the fourth minute. The data indicate that the normal insulin response to an enterically administered glucose stimulus is a smoothly rising uniphasic one, in contrast to the typical biphasic insulin response to a "square-wave" intravenous glucose stimulus.

Dynamic evaluation of prolactin secretion in essential hypertension: evidence against hypothalamic-pituitary dopaminergic dysfunction.

Hyperprolactinemia has previously been noted in patients with essential hypertension and it has been suggested that the increased PRL levels in this condition may reflect reduced central dopaminergic activity. In the present study, PRL secretion was evaluated in 17 patients with essential hypertension and in 9 normal controls as an indirect index of hypothalamic-pituitary dopaminergic activity. PRL levels were measured basally, at night, and after TRH (200 micrograms, iv), metoclopramide (10 mg, orally), and L-dopa (500 mg, orally). Basal PRL levels were similar in both groups [essential hypertension, 301.2 +/- 176.2 microunits/ml; controls, 334.2 +/- 98.8 microunits/ml (mean +/- SD)]. No differences in PRL levels were found after TRH, L-dopa, and metoclopramide or during sleep between the 2 groups. When the patients were classified according to their PRA, no differences were noticed in either basal levels or the patterns of PRL response. It is concluded that PRL secretion is normal in patients with essential hypertension, which could be indirect evidence against reduced hypothalamic-pituitary dopaminergic activity in this disease. However, minor abnormalities not detected by PRL measurements could be involved in the pathogenesis of essential hypertension.

Peripheral dopaminergic blockade for the treatment of diabetic orthostatic hypotension.

This study was designed to evaluate the effects of domperidone, a peripheral dopaminergic antagonist, in diabetic patients with symptomatic orthostatic hypotension. Nine patients were admitted to the hospital, placed on a diet containing 150 mEq sodium, and studied for periods of 4 hours, on different days, in the following conditions: (1) supine position, (2) upright posture (UP), (3) UP after 10 mg domperidone, intravenously in bolus, and (4) UP after 3 days of domperidone, 30 mg orally. Before domperidone the mean blood pressure observed in supine position of 132 +/- 37/75 +/- 6 mm Hg fell to 75 +/- 22/57 +/- 13 mm Hg after 2 hours in UP. Acute domperidone did not change the blood pressure response to UP. After 3 days of oral domperidone and in UP for 2 hours, the mean blood pressure value of 89 +/- 21/61 +/- 8 mm Hg was higher than that before domperidone (p less than 0.05), with relief of symptoms in all patients. This blood pressure response to UP has been maintained in six patients who completed 6 months of therapy. No differences were observed in plasma renin activity, aldosterone, sodium, and potassium and in 4-hour urinary excretion of aldosterone, epinephrine, norepinephrine, and dopamine, determined during the UP tests. Administration of domperidone for 3 days reduced the falls in creatinine clearance and the urinary excretion of sodium and potassium induced by UP but did not alter the blood pressure and aldosterone dose-response curves to angiotensin II. Although the mechanism of action is not defined, it is concluded that domperidone is effective for the treatment of orthostatic hypotension in patients with diabetes.

Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic beta-cell demand in men.

Low levels of sex hormone-binding globulin (SHBG) are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic beta-cell demand (e.g. obesity) both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic beta-cell secretion in men with different body compositions. Eighteen young men (30.0 +/- 2.4 years) with normal glucose tolerance and body mass indexes (BMI) ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g) and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P < 0.05), proinsulin (r = -0.47, P < 0.05), C-peptide (r = -0.55, P < 0.05) and also with proinsulin at 120 min after glucose load (r = -0.58, P < 0.05). Stepwise regression analysis revealed that proinsulin values at 120 min were the strongest predictor of SHBG (r = -0.58, P < 0.05). When subjects were divided into obese (BMI > 28 kg/m2, N = 8) and nonobese (BMI < or = 25 kg/m2, N = 10) groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic beta-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic beta-cell demand.

Relationship between insulin antibodies and metabolic control in type I diabetes mellitus.

1. The objective of the present study was to investigate whether a change in insulin therapy from bovine to purified porcine insulin would result in a decreased level of insulin antibodies (IA) in type I diabetic patients and whether there would be better metabolic control. 2. Insulin antibodies were measured by ELISA. Fifteen type I diabetic patients were prospectively followed for 8 months with monthly evaluations after changing insulin therapy from bovine to purified porcine insulin. 3. Group I patients (N = 4) had IA greater than or equal to 1.5 (value obtained by dividing the ELISA absorbance of the tested serum by the absorbance of a standard serum) at the beginning of the study. For group I patients, the modification of insulin therapy caused a 57% reduction in insulin antibody levels, and this reduction was correlated with a decrease in 24-hour glycosuria (rs = 0.66, P less than 0.001) and glycated protein (rs = 0.65, P less than 0.01). Group II patients (N = 8) had IA less than 1.5 and greater than or equal to 0.3 and group III (N = 3) had IA less than 0.3. Insulin antibody levels were unchanged during the follow-up period in both group II and group III. 4. We also studied endogenous insulin secretion, measured as fasting C-peptide, and its relationships with metabolic control and insulin antibody levels. Patients with residual insulin secretion (C-peptide greater than 60 pmol/l) showed lower levels of 24-h glycosuria, glycated protein and glycated hemoglobin. Furthermore, in this group of patients a negative correlation was found between C-peptide and insulin antibody levels (rs = -0.36, P less than 0.01). 5. We conclude that insulin antibodies could be one of the factors having a detrimental effect on metabolic control.

Effect of positive pressure breathing on plasma antidiuretic hormone and renal function in dogs.

The effect of intermittent mechanical ventilation and positive end-expiratory pressure on plasma antidiuretic hormone concentration was determined in 14 pentobarbital anesthetized dogs. The study was divided into a control period (spontaneous respiration), and two consecutive 30 and 60 min periods after the start of controlled respiration: Group I - intermittent positive breathing (IPPB); Group II - positive end-expiratory pressure (PEEP) with 5 cm H2O. A decrease in urinary flow (36.9%) was observed during end-expiratory pressure breathing. An increase in plasma antidiuretic hormone in group II from 4.5 +/- 2.4 to 24.6 +/- 16.0 pg/ml (P less than 0.01) was associated with a significant reduction of free water clearance from 1.2 +/- 0.6 to 0.3 +/- 0.4 ml/min and an increase of the urine/plasma osmolality ratio (143%, P less than 0.05). The decrease in urinary output and concurrent reduction of urinary sodium excretion also suggest an influence of the fall in glomerular filtration rate and renal plasma flow on renal function. IPPB only reduced total Na+ and K+ excretion. These results indicate that the mechanisms underlying the renal response to positive end-expiratory pressure breathing may be due to an increase in antidiuretic hormone plasma levels leading to a fall in urinary flow and in part to a decrease in sodium excretion.

Prevalence of autoantibodies in simplex and multiplex families of Brazilian insulin-dependent diabetic patients.

1. Forty-one simplex and 6 multiplex families of Brazilian IDDM patients were studied by the indirect immunofluorescence technique to determine the prevalence of the following autoantibodies: islet cells (ICA), islet cells which fix complement (ICA-CF), thyroid microsomes (TMA), thyroglobulin (TGA), and gastric-parietal cells (PCA). A total of 54 IDDM patients belonging to two family groups were analyzed. 2. A significantly higher frequency of ICA-CF and TMA was detected among the siblings from multiplex families than among those from simplex families (18.7% vs 1.7%). 3. A prospective study of 5 ICA-positive siblings was undertaken, and 2 who later became diabetic were found to be positive to both ICA and ICA-CF. 4. The prevalence of islet-cell antibodies in these 54 Brazilian IDDM patients and their unaffected first-degree relatives from genetically mixed groups suggests that the humoral autoimmune mechanisms of the disease are probably identical to those observed in other populations of different ethnic backgrounds.

Nocturnal urinary growth hormone excretion as a criterion for growth hormone deficiency.

Nocturnal urinary growth hormone (U-hGH) levels measured by a sensitive immunoenzymometric assay were compared with hGH levels in serum before and after a clonidine test in healthy children and in children with short stature to determine whether U-hGH measurement is useful for the screening of hGH deficiency. The study was carried out on 19 healthy children (10 prepubertal and 9 pubertal subjects) and on 20 children with short stature, 10 with growth hormone deficiency (hGHD) and 10 with constitutional growth retardation. The diagnosis of hGHD was based on a blunted response to two provocative hGH tests in the appropriate clinical setting. Overnight urinary hGH secretion (mean of 3 collections) was measured by an immunoenzymometric assay. The best discrimination was obtained when the results were expressed as ng/h. Only one individual in the prepubertal group (U-hGH, 0.05 ng/h) and one patient in the growth retardation group (U-hGH, 0.08 ng/h) had a urinary hGH value below the highest value (0.17 ng/h) observed in the growth hormone deficiency group. The coefficient of correlation between urinary hGH in ng/h and post-clonidine peak was 0.50 (P = 0.0015), between urinary hGH in ng/l and post-clonidine peak was 0.48 (P = 0.0025), between urinary hGH in ng/l per hour and post-clonidine peak was 0.47 (P = 0.0027). The highest specificity (0.93), sensitivity (0.90), false negative rate (0.96) and false positive rate (0.82) were obtained when U-hGH was expressed as ng/h per night. Measurement of urinary nocturnal hGH excretion is a useful, simple, noninvasive method for the diagnosis of hGH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory effect of calcitonin on growth hormone response to growth hormone releasing hormone in acromegaly.

1. A neuroendocrine role for calcitonin (CT) has been suggested by the finding of CT receptors in the hypothalamus. We have recently shown that salmon calcitonin (sCT) inhibits growth hormone releasing hormone (GHRH)-induced GH secretion in man by a mechanism apparently independent of changes in peripheral cortisol, glucose, calcium or parathyroid hormone levels. 2. We have further investigated the inhibitory action of sCT on GH secretion by studying the effects of sCT (100 MRC units, im) or placebo on basal and GHRH (1-29) NH2 (50 micrograms, iv) stimulated GH secretion in 6 acromegalic patients with active disease. 3. Basal GH levels were not altered by sCT administration (placebo: 136 +/- 99 micrograms/l vs sCT: 99 +/- 53 micrograms/l). However, the GH response to GHRH was decreased by sCT. The area under the curve was significantly smaller when patients were treated with sCT compared to placebo controls (placebo: 77202 +/- 57036 vs sCT: 64828 +/- 51909 micrograms min-1 l-1; P less than 0.02). No changes in glucose or calcium levels were observed. 4. These results demonstrate that sCT decreases GHRH-induced GH secretion in acromegalic patients. Although the mechanism of action of sCT on GH secretion is unknown, our results indicate that the inhibitory effect of this peptide on GH secretion is also observed in patients harboring pituitary adenomas.

Influence of dexamethasone and weight loss on the regulation of serum leptin levels in obese individuals.

The adipocyte hormone leptin is thought to serve as a signal to the central nervous system reflecting the status of fat stores. Serum leptin levels and adipocyte leptin messenger RNA levels are clearly increased in obesity. Nevertheless, the factors regulating leptin production are not fully understood. The aim of this study was to determine the effects of in vivo administration of the synthetic glucocorticoid dexamethasone and weight loss on serum leptin levels in two independent protocols. Twenty-five obese subjects were studied (18 women and 7 men, mean age 26.6 +/- 6 years, BMI 31.1 +/- 2.5 kg/m(2), %fat 40.3 +/- 8.3) and compared at baseline to 22 healthy individuals. Serum levels of leptin, insulin, proinsulin and glucose were assessed at baseline and after ingestion of dexamethasone, 4 mg per day (2 mg, twice daily) for two consecutive days. To study the effects of weight loss on serum leptin, 17 of the obese subjects were submitted to a low-calorie dietary intervention trial for 8 weeks and again blood samples were collected. Serum leptin levels were significantly higher in the obese group compared to the control group and a high positive correlation between leptinemia and the magnitude of fat mass was found (r = 0.88, P<0.0001). After dexamethasone, there was a significant increase in serum leptin levels (22.9 +/- 12.3 vs 51.4 +/- 23.3 ng/ml, P<0.05). Weight loss (86.1 +/- 15.1 vs 80.6 +/- 14.2 kg, P<0.05) led to a reduction in leptin levels (25.13 +/- 12.8 vs 15.9 +/- 9.1 ng/ml, P<0.05). We conclude that serum leptin levels are primordially dependent on fat mass magnitude. Glucocorticoids at supraphysiologic levels are potent secretagogues of leptin in obese subjects and a mild fat mass reduction leads to a disproportionate decrease in serum leptin levels. This suggests that, in addition to the changes in fat mass, complex nutritional and hormonal interactions may also play an important role in the regulation of leptin levels.

Clinical trial of Myrcia uniflora and Bauhinia forficata leaf extracts in normal and diabetic patients.

1. Myrcia uniflora and Bauhinia forficata were compared with placebo for their hypoglycemic effect in randomized cross-over double-blind studies in 2 groups of normal subjects (10 subjects each) and 2 groups of Type II diabetic patients (18 in the M. uniflora group and 16 in the B. forficata group). The protocol with each plant lasted 56 days. 2. After the ingestion of infusions of 3 g leaves/day of M. uniflora and B. forficata leaves, no acute or chronic effects on plasma glucose levels or glycated hemoglobin were found in either group. However, plasma insulin levels in the diabetic group were lower after M. uniflora than after placebo. 3. Among other clinical parameters tested, a statistically significant difference was found only in the alkaline phosphatase level after placebo compared with that after M. uniflora in the normal group. 4. There were no differences in any clinical parameters after the use of placebo or of B. forficata. 5. We conclude that infusions prepared from the leaves of M. uniflora or B. forficata have no hypoglycemic effect on normal subjects or Type II diabetic patients.

Non-obese adult onset diabetes with oral hypoglycemic agent failure: islet cell autoantibodies or reversible beta cell refractoriness?

Pancreatic beta cell function and insulin sensitivity, analyzed by the homeostasis model assessment, before and after 24 weeks of insulin therapy were studied and correlated with the presence of autoantibodies against beta cells (islet cell and anti-glutamic acid decarboxylase antibodies), in a group of 18 Brazilian lean adult non-insulin-dependent diabetes mellitus (NIDDM) patients with oral hypoglycemic agent failure (OHAF). Median fasting plasma glucose before and after insulin treatment was 19.1 and 8.5 mmol/l, respectively (P < 0.001); median HbA1c was 11.7% before vs 7.2% after insulin treatment (P < 0.001). Forty-four percent of the patients were positive (Ab+) to at least one autoantibody. Fasting C-peptide levels were lower in Ab+ than Ab- patients, both before (Ab+: 0.16+/-0.09 vs Ab-: 0.41+/-0.35 nmol/l, P < 0.003) and after insulin treatment (Ab+: 0.22+/-0.13 vs Ab-: 0.44+/-0.24 nmol/l, P < 0.03). Improvement of H was seen in Ab- (median before: 7.3 vs after insulin therapy: 33.4%, P = 0.003) but not in Ab+ patients (median before: 6.6 vs after insulin therapy: 20.9%). These results show that the OHAF observed in the 18 NIDDM patients studied was due mainly to two major causes: autoantibodies and beta cell desensitization. Autoantibodies against beta cells could account for 44% of OHAF, but Ab- patients may still present beta cell function recovery, mainly after a period of beta cell rest with insulin therapy. However, the effects of beta cell function recovery on the restoration of the response to oral hypoglycemic agents need to be determined.

Latent autoimmune diabetes of the adult (LADA) in a Brazilian Indian.

CONTEXT: Latent autoimmune diabetes of the adult (LADA) as originally described represents perhaps as many as 10 - 20% of adult-onset patients with diabetes. DESIGN: case report. CASE REPORT: A 38-year-old Brazilian Xavante-Jê Indian with Latent Autoimmune Diabetes of the Adult (LADA) is described, coming from the Sangradouro community in Poxoréu, Mato Grosso. The onset of diabetes after reaching 25 years of age, the evolution to insulin deficiency after a period of insulin-independence and the presence of auto-antibodies to glutamic acid decarboxylase (GAD) characteristic of LADA were present. This patient may represent the first case of LADA in a Brazilian with full Indian heritage. Further studies are necessary to verify the prevalence of this new type of diabetes in this population that does not have Caucasoid admixture and has a particular environmental background.

[Progression to IDDM and islet cell antibodies (ICA; ICA-CF)]. / Estudo de auto-anticorpos para ilhotas pancreáticas (ICA e ICA-CF) e evolução para o diabetes insulino-dependente (DM ID).

We have followed eight first-degree relatives of IDDM patients (insulin-dependent, type I diabetes) attending the outpatient diabetes clinic at the State University of Rio de Janeiro for three years, all of them with positive islet cell antibodies (ICA and/or ICA-CF). Three out of eight relatives less than fifteen years old have subsequently progressed to overt Insulin-Dependent Diabetes Mellitus (IDDM) 12, 21 and 8 months after the first positive autoantibodies detection. Four relatives have remained with ICA and/or ICA-CF positive, and in another one the reaction became negative during the observation period. A positive correlation has been found between high titles of ICA (> or = 1/16) and development of IDDM. We have concluded from our prospective study during three years that of our antibody-positive relatives, 37.5 % have developed overt diabetes, all of them being less than fifteen years old, with high titles of ICA and ICA-CF positive.

[Insulin transference in 198 patients from 6 Latin American countries]. / Transferencia de insulinas en 198 pacientes de seis países latinoamericanos.

A multicentric, comparative, single-blind, randomized, prospective study was designed to evaluate the efficacy and safety of the transference from animal source insulins to rDNA human insulin in Latinamerican insulin-requiring diabetic patients. All the patients were on animal insulin for at least two months before inclusion. The patients were evaluated at the beginning, and at two and six weeks after inclusion. A total 198 patients completed the study and were considered evaluable: 94 were assigned to the animal insulin group, and 104 to the human insulin group. There were no statistically significant baseline differences between groups. The only statistically significant difference, detected at the end of the study, was a reduction in fasting blood glucose level in the human insulin group (animal insulin 212 +/- 95.3 initial vs 193 +/- 78.3 mg/dL final, p = 0.18; human insulin 198 +/- 86.8 vs 169 +/- 71.7, p = 0.025). There were no statistically significant initial-final changes in the rest of the parameters evaluated although a trend of reduction in glycohemoglobin levels was observed in both groups. There were more episodes of mild hipoglycemia in the human insulin group, and only one episode of severe unwarned hypoglycemia in the same group. We conclude that the transference of insulins in Latinamerican diabetic patients is effective and reasonably safe (with a dose adjustment when the change is made).

[Diabetic ketoacidosis induced by immunologic insulin resistance]. / Cetoacidose diabética desencadeada por resistência imunológica à insulina.

Although rare, ketoacidosis may be induced by the occurrence of antibody mediated insulin resistance. Cases of 3 patients with ketoacidosis precipitated by immunologic insulin resistance (IIR) are reported. CASE REPORT--Three patients were admitted to the primary care unit of Hospital São Paulo in Diabetic Ketoacidosis. Demographic data of the patients (HML, DRJ and DIS) included: age (46.39 and 54 y.o.); sex (2F, 1M); diabetes mellitus (2 DM II and 1 pancreatic); duration of diabetes (6, 11 and 9 years) and BMI (17.5; 25.5 and 24.3 kg/m2. Admission laboratory data were: glucose (40, 38 and 22 mmol/L); pH (7.2; 6.9 and 7.2) and all had ketonuria. Insulin requirements for metabolic control were: HML: 1494U; DRJ: 1496U; DIS: 450U in a period of: 212, 206 and 72h. The plasmatic leves of Anti insulin antibodies (IA) measured by RIA (nU/mL) and ELISA (EI), where: HML: 7186, 3.26; DRJ: 7879, 3.42 and DIS: 8377, 2.88. HI was associated with marked decrease of both, insulin requirements and IA (HML: 3393, 1.39 after 10 months and DRJ: 4673, 2.34; DIS: 1510, after 18 months) at follow-up. DISCUSSION--The High Insulin requirements and time necessary to achieve the metabolic control guided us to the diagnosis of IIR. It was confirmed by high levels of AI and by the improvement in the metabolic control after the introduction of HI. CONCLUSION--The physician must be alert to severe IIR if there is no response after standard therapy to ketoacidosis. HI can be considered a valid alternative of treatment for IIR.