Mauro Boronat

Differences in cardiovascular risk profile of diabetic subjects discordantly classified by diagnostic criteria based on glycated hemoglobin and oral glucose tolerance test

OBJECTIVE To characterize the cardiovascular risk profile of subjects categorized differently by A1C- and oral glucose tolerance test (OGTT)-based diagnostic criteria for diabetes according to the recommendations of the American Diabetes Association (ADA). RESEARCH DESIGN AND METHODS An OGTT, A1C, and several cardiovascular risk factors were assessed in 964 individuals without known diabetes participating in a cross-sectional epidemiological survey in Gran Canaria, Spain. RESULTS Taking the OGTT as the gold standard, the sensitivity and specificity of an A1C value ≥6.5% were 38.7 and 99.6%, respectively. Subjects who fulfilled A1C-based criterion presented greater measures of BMI and waist circumference, lower values for HDL cholesterol, and higher values for fasting plasma glucose, homeostasis model assessment of insulin resistance, and fibrinogen than subjects with diabetic OGTT but A1C <6.5%. CONCLUSIONS Newly diagnosed diabetic individuals who fulfill A1C-based diagnostic criterion for the disease display a more unfavorable cardiovascular risk profile than individuals who only meet the glucose-based criteria.

Successful outcome of pregnancy in a patient with Cushing's disease under treatment with ketoconazole during the first trimester of gestation

Background. Ketoconazole is the most widely used medical treatment for Cushings syndrome, but, because of its potential to cause birth defects, it is not recommended during pregnancy. Specifically, due to its antiandrogenic effects, ketoconazole entails theoretical risks of interfering with the development of external genitalia in male fetuses. Case. A pregnancy was diagnosed at 13 weeks of gestation in a 26-year-old woman with Cushings disease under treatment with ketoconazole. The drug was withdrawn and the patient underwent transsphenoidal surgery at 16 weeks of pregnancy. She did not develop postsurgical adrenal insufficiency and was treated with metyrapone during the second and third trimesters of gestation. Partum was induced at 34 weeks of pregnancy. The patient delivered a healthy male infant with normal external genitalia. Conclusion. Treatment with ketoconazole during the critical period of organogenesis did not cause congenital birth defects to the male fetus of a woman with Cushings disease. This report should be taken into account for future cases of unplanned pregnancies in women with Cushings syndrome treated with ketoconazole, as well in those cases in which other therapeutic options are not feasible.

Disproportionately high incidence of diabetes-related end-stage renal disease in the Canary Islands. An analysis based on estimated population at risk

BACKGROUND An exceptionally high incidence of diabetes-related end-stage renal disease (DM-ESRD) has been reported in the Canary Islands. This phenomenon was attributed to an increased prevalence of diabetes in this community. We compared the incidence of DM-ESRD in the Canary Islands with the rest of Spain among the estimated number of individuals at risk (people with diabetes in the population). METHODS The population-at-risk was calculated using census population figures and estimates of self-reported diabetes prevalence from the Spanish National Health Survey in the years 2003 and 2006. The incidence of DM-ESRD for the same years was obtained through Spanish regional registries. The independent effect of age, community of residence and calendar year was estimated with a Poisson regression model. Age-standardized acceptance rate ratios were calculated for each community. RESULTS Overall DM-ESRD incidence in the Canary Islands population-at-risk was 1209.9 per million population (pmp) in 2003 and 1477.3 pmp in 2006. Rates for the remaining Spanish regions ranged from 177.3-984.9 pmp. The incidence was higher in the Canary Islands across all age groups, but was most striking for patients > or =75 years. Diabetes prevalence in the general population was greater in the two youngest age strata and diminished from 75 years on in the Canary Islands, in comparison with other areas of Spain. Using a cluster of three communities with the lowest incidence as a reference, the relative risk of DM-ESRD in the Canary Islands population-at-risk was 3.88 [95% confidence interval (CI): 3.07-4.89]. Age-standardized acceptance ratios (95% CI) in the Canary Islands were 2.21 (1.85-2.61) in 2003 and 2.73 (2.34-3.17) in 2006. CONCLUSIONS Individuals with diabetes in the Canary Islands present a disproportionately high incidence of ESRD. Diabetic Canary inhabitants are exposed to the disease for a longer time and therefore, may be more vulnerable to the development of chronic diabetes complications, including ESRD.

Mumps Orchitis in the Post-vaccine Era (1967-2009): A Single-center Series of 67 Patients and Review of Clinical Outcome and Trends

Since the introduction of the mumps vaccine, the age of appearance of mumps infection has shifted from children to adolescents and young adults, groups with a higher incidence of disease complications and sequelae. During the years 2000-2001, the Gran Canaria Island was part of an epidemic of mumps. In that period, our institution attended 67 cases of serologically confirmed acute mumps orchitis, the most serious complication of mumps infection in young postpubertal males. We conducted a descriptive and prospective study of this cohort and extensively reviewed the literature from 1967 (the year the first mumps vaccine was introduced) to 2009. Fifty-six patients were admitted because of general impairment and were treated with alpha-interferon. Sixty-six patients presented parotitis previous to orchitis (interval from parotitis to orchitis, 4.9 d). Orchitis was unilateral in 89.5% and bilateral in 10.4% of cases. More than 98% of patients had orchitis-associated fever. Nine patients had clinical and biochemical data showing acute mumps meningitis, and 11 had subclinical pancreatitis. The mean duration of symptoms was 4.6 days (range, 1-9). During the acute phase, more than 41% of the evaluated testes had a volume >25 mL. Acute hormonal disturbances were highly prevalent. These included decreased levels of testosterone and inhibin B with low or normal levels of gonadotropins in 35% of subjects, and, to our knowledge not previously reported, an atypical hormonal pattern consisting of low levels of free testosterone and inhibin B, along with increased measures of luteinizing hormone but low or normal follicle-stimulating hormone levels (11% of cases). During the follow-up period (mean, 331 d) a high incidence of sperm disturbance was found. Abbreviations: CRP = C-reactive protein, CSF = cerebrospinal fluid, ESR = erythrocyte sedimentation rate, FSH = follicle-stimulating hormone, LH = luteinizing hormone, MMR = measles, mumps, and rubella triple vaccine, NSAID = nonsteroidal antiinflammatory drugs, WHO = World Health Organization.

High levels of lipoprotein(a) are associated with a lower prevalence of diabetes with advancing age: Results of a cross-sectional epidemiological survey in Gran Canaria, Spain

BackgroundRecent data suggest that concentrations of lipoprotein(a) [Lp(a)] may be inversely associated with the risk of diabetes. This study analyzed the relationships between Lp(a) and both diabetes and insulin resistance in an adult cohort from the island of Gran Canaria, Spain.MethodsLp(a), homeostasis model assessment for insulin resistance (HOMA-IR) and conventional risk factors for diabetes were assessed in a sample of 1,030 adult individuals participating in a cross-sectional population-based epidemiological survey in the city of Telde. Diabetes was defined according to the WHO 1999 criteria, or as a previous diagnosis of diabetes. To identify patients at risk for diabetes, an Lp(a) cutoff level of 46 mg/dl was selected previously using classification and regression tree analysis. A multivariate logistic regression model with L2-regularization was used to assess the independent effect of Lp(a) on diabetes and its interactions with variables traditionally linked to the disease. Additionally, to investigate the effect of Lp(a) on insulin resistance, a parametric model was developed to describe the relationship between age and HOMA-IR values in subjects with levels of Lp(a) ≤46 or >46 mg/dl.ResultsAlong with variables known to be associated with diabetes, including age, mean blood pressure, serum triglycerides, and an interaction term between age and low HDL cholesterol, the logistic model identified a significant inverse association for diabetes and the interaction term between age and Lp(a) levels >46 mg/dl. According to the proposed parametric model, HOMA-IR was significantly lower in subjects of all ages who had Lp(a) levels >46 mg/dl.ConclusionsThese results suggest that the age-related increase in the probability of having diabetes is significantly lower in subjects with Lp(a) levels >46 mg/dl. This could be explained in part by a lower insulin resistance in this subset of the population.

Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus.

Abstract Urinary albumin excretion has been consistently found to be normal in a significant number of subjects with early stages of diabetic kidney disease. This study was aimed to estimate the prevalence and characteristics of non-albuminuric chronic kidney disease associated with type 2 diabetes mellitus among subjects who reach advanced stages of renal failure. Study population was composed of incident patients with advanced chronic kidney disease (glomerular filtration rate <30 mL/min) related to type 2 diabetes in a tertiary hospital from Gran Canaria (Spain) during a period of 2 years. Subjects were classified as normoalbuminuric (urinary albumin-to-creatine ratio [UACR] <30 mg/g), microalbuminuric (UACR ≥30 and <300 mg/g), or proteinuric (UACR ≥300 mg/g). Of 78 eligible patients, 21.8% had normoalbuminuria, 20.5% had microalbuminuria, and 57.7% had proteinuria. Individuals with normoalbuminuria were mostly women and had a lower prevalence of smoking and polyneuropathy than subjects with microalbuminuria or proteinuria. They also presented greater measures of body mass index and waist circumference, higher values of total and LDL cholesterol, and lower values of HbA1c and serum creatinine than subjects with microalbuminuria or proteinuria. Multivariate analysis demonstrated that female sex (positively) and HbA1c and polyneuropathy (negatively) were independently associated with absence of albuminuria. In conclusion, around 20% of subjects with diabetes-related advanced chronic kidney disease, characteristically women, have normal urinary albumin excretion. HbA1c and polyneuropathy are inversely related to this non-albuminuric form of nephropathy.

Severe deterioration of metabolic control caused by malfunction of a disposable insulin pen device.

This report describes the case of a 68-yr-old diabetic woman with severe deterioration of glycemic control caused by the use of a malfunctioning insulin pen device.

Relationship between Anemia and Serum Concentrations of Calcium and Phosphorus in Advanced Non-Dialysis-Dependent Chronic Kidney Disease

Background/Aims: Different biochemical abnormalities of metabolic bone disease have been associated with anemia of chronic kidney disease (CKD), mainly in hemodialysis patients. However, all of these abnormalities are closely inter-related and their individual effect on the development of anemia is uncertain. This study was aimed to assess the relationship between anemia and a set of metabolic bone disease biomarkers in a cohort of adult patients with advanced non-dialysis-dependent CKD. Methods: The sample consisted of 382 patients submitted to a Nephrology Unit for evaluation of advanced CKD in a tertiary hospital from Gran Canaria during 3 years. Associations between anemia and serum levels of calcium (albumin-corrected), phosphorus, PTH, 25-hydroxivitamin D (25(OH)D3) and alkaline phosphatase were analyzed by using logistic regression models with adjustment for other demographic, clinical and biochemical covariates potentially related to anemia and to bone mineral metabolism. Results: Serum levels of calcium and 25(OH)D3 (negatively) and phosphorus (positively) were significantly associated with anemia in an unadjusted logistic regression model. In a fully adjusted multivariable model, the OR for anemia was 0.29 (95% CI 0.16-0.49; p < 0.0001) for every 1 mg/dl increase in serum calcium and 2.19 (95% CI 1.55-3.15; p < 0.001) for every 1 mg/dl increase in serum phosphorus. Female sex and lower serum albumin levels were also independently associated with anemia. The inclusion of albumin in the adjusted model displaced the significance of 25(OH)D3. Conclusions: Circulating levels of calcium and phosphorus are strongly linked to anemia in patients with advanced non-dialysis CKD.

Suspension of basal insulin to avoid hypoglycemia in type 1 diabetes treated with insulin pump

Summary Treatment with continuous s.c. insulin infusion (CSII) provides better glycemic control and lower risk of hypoglycemia than conventional therapy with multiple daily insulin injections. These benefits have been related to a more reliable absorption and an improved pharmacokinetic profile of insulin delivered through CSII therapy. However, even for patients treated with CSII, exaggerated postmeal hyperglycemic excursions and late postabsorptive hypoglycemia can still constitute a therapeutic challenge. Two female patients with type 1 diabetes who began treatment with CSII required to increase their previous breakfast insulin-to-carbohydrate ratio in order to achieve postprandial glycemic goals. However, they simultaneously presented recurrent episodes of late hypoglycemia several hours after breakfast bolus. Advancing the timing of the bolus was ineffective and bothersome for patients. In both cases, the best therapeutic option was to set a basal insulin rate of zero units per hour during 6 h after breakfast. Even so, they need to routinely take a midmorning snack with 10–20 g of carbohydrates to avoid late postabsorptive hypoglycemia. They have been using this insulin schedule for about 3 years without complications. The action of prandial insulin delivered through insulin pumps can be inappropriately delayed for the requirements of some patients. Although suspension of basal rate can be an acceptable therapeutic alternative for them, these cases demonstrate that new strategies to improve the bioavailability of prandial insulin infused through CSII are still needed. Learning points CSII remains the most physiologically suitable system of insulin delivery available today. Additionally, the duration of action of prandial insulin delivered through insulin pumps can be excessively prolonged in some patients with type 1 diabetes. These patients can present recurrent late episodes of hypoglycemia several hours after the administration of insulin boluses. The routine suspension of basal insulin for several hours, leaving meal bolus to cover both prandial and basal insulin requirements, can be a therapeutic option for these subjects.

Combined treatment with GH and anastrozole in a pubertal boy with Cushing's disease and postsurgical GH deficiency

Growth failure is a characteristic manifestation of pediatric Cushings disease. Catch-up growth is usually incomplete after cure of the disease, and final height is often compromised. Possible mechanisms for this phenomenon include postoperative persistence of GH hyposecretion and absence of retardation of bone maturation in spite of GH deficiency. This report describes the outcome in the case of a boy with Cushings disease for whom GH replacement therapy was combined with anastrozole, an aromatase inhibitor, in order to delay skeletal maturation and extend the available time for linear growth. The case of a 14 years 4-months-old pubertal male (Tanner stage III) with GH deficiency after successful surgical treatment of Cushings disease is presented. His height was 147.2 cm (-2.34 SDS), and his midparental target height 171.2 cm (-0.95 SDS). Bone age was 13.5 years and predicted adult height 163.2 cm (-2.2 SDS). Combined treatment was administered for 2.5 years. GH was maintained up to age 18 years. Anastrozole induced a substantial deceleration of bone age. Near-final height at 18 years was 169.5 cm (-1.07 SDS). Puberty progressed normally. Compared with population reference data, bone mineral density before GH plus anastrozole treatment was -4.07 SDS in the lumbar spine and -1.85 SDS in the femoral neck. These measures increased to -1.95 and -0.89 SDSs respectively, at 18 years, when GH was discontinued. Combined treatment with GH and aromatase inhibitors could be a therapeutic alternative to improve the stature of pubertal boys with Cushings disease and postsurgical GH deficiency.