Juan A. Rull

Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy. A double-blind cross-over study

A controlled clinical trial on the efficacy of a nortriptyline-fluphenazine combination was carried out in patients with painful diabetic polyneuropathy. A visual analog scale was used to evaluate the relief of pain or paresthesia. Significant relief of both pain and paresthesia was obtained with this combination. The differences were statistically significant. Side effects were frequent but not usually severe enough to lead to cessation of these medications.

Prevalence of dyslipidemias in the Mexican National Health and Nutrition Survey 2006

OBJECTIVE To describe the prevalence of lipid abnormalities found in the Mexican National Health and Nutrition Survey 2006 (ENSANut 2006). MATERIAL AND METHODS Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9- to 12-hour fast. RESULTS Median lipid concentrations were: cholesterol 198.5 mg/dl, triglycerides 139.6 mg/dl, HDL-cholesterol 39.0 mg/dl, non-HDL-cholesterol 159.5 mg/dl and LDL-cholesterol 131.5 mg/dl. The most frequent abnormality was HDL-cholesterol below 40 mg/dl with a prevalence of 60.5% (95%CI 58.2-62.8%). Hypercholesterolemia (> 200 mg/dl) had a frequency of abnormality of 43.6% (95%CI 41.4-46.0%). Only 8.6% of the hypercholesterolemic subjects knew their diagnosis. Hypertriglyceridemia (>or= 150 mg/dl) was observed in 31.5% (IC 95% 29.3-33.9%) of the population. CONCLUSIONS The ENSANUT 2006 data confirm that the prevalence of hypoalphalipoproteinemia and other forms of dyslipidemia in Mexican adults is very high.

Diseases and problems secondary to massive obesity.

Morbid obesity is a health hazard. It carries several health risks and decreases life expectancy. Individuals with morbid obesity may develop one or more complications. These are mainly cardiovascular, metabolic, respiratory, gastrointestinal, renal, genitourinary and gynaecological. Patients with morbid obesity also have a high surgical risk. This review analyses the most common complications of morbidly obese patients and their changes after surgically induced weight loss.

Levels of Plasma Insulin During Cortisone Glucose Tolerance Tests in “Nondiabetic” Relatives of Diabetic Patients: Implications of Diminished Insulin Secretory Reserve in Subclinical Diabetes

Plasma levels of insulin were determined during standard oral glucose tolerance tests and during cortisone glucose tolerance tests performed upon “nondiabetic” subjects (normal standard GTT) who were first degree relatives of diabetic patients. The standard test was also performed upon mildly diabetic patients and healthy control subjects. The results of the standard glucose tolerance test (levels of plasma insulin and blood glucose) did not differentiate the relatives with positive cortisone glucose tolerance tests (subclinical diabetes) from those with negative cortisone glucose tolerance tests although in both groups levels of plasma insulin were lower than in healthy subjects. However, the results of the cortisone glucose tolerance test did distinguish the group with subclinical diabetes from the relatives with negative tests since the secretion of insulin was delayed and insufficient in the subjects with positive testsl During the standard test patients with mild “maturityonset” diabetes showed delayed and insufficient secretion of insulin as compared to the healthy subjects. It is concluded that during the cortisone glucose tolerance test, “nondiabetic” relatives of diabetic patients who have positive tests (subclinical diabetes) exhibit a defect in the secretion of insulin which distinguishes them from subjects with negative tests. This defect is similar in pattern to that observed in mildly diabetic patients during the standard test. This deficiency in the secretion of insulin represents an important part of the mechanism which induces a positive cortisone glucose tolerance test. This demonstration that, in some relatives of diabetics, a grossly normal standard glucose tolerance can exist at a time when decreased reserve insulin secretory capacity can be measured, justifies a careful evaluation of whether some form of therapy is indicated at this stage of the disease (subclinical diabetes) and, if so, what form it should be. The meaning of the statistically significant subnormal response of plasma insulin to a standard glucose load in relatives with negative cortisone glucose tests is not yet apparent. Since in them the reserve insulin secretory capacity, as measured by the CGTT, remains intact, it is premature, pending additional data, to raise the question of possible treatment of this group.

Locus on Chromosome 6p Linked to Elevated HDL Cholesterol Serum Levels and to Protection Against Premature Atherosclerosis in a Kindred With Familial Hypercholesterolemia

Abstract— Heterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extended multigenerational kindred with FH linked to chromosome 1p32 in which atherosclerotic complications were either delayed or prevented in individuals with elevated HDL cholesterol (HDL-C) levels or hyperalphalipoproteinemia (HA). Premature CHD was observed in FH individuals without HA. The study of this family established that the HA trait in the family also followed an autosomal dominant mode of inheritance with a pattern of segregation independent from FH. We identified a locus on chromosome 6 linked to elevated HDL-C levels (HA) in this family. Haplotype analysis refined the localization to a 7.32-cM interval (73 to 80 cM from pter) flanked by markers D6S1280 and D6S1275. Parametric 2-point and multipoint analyses yielded maximum LOD scores of 3.05 and 3.17, respectively. This finding was confirmed with a nonparametric multipoint score of 3.78 (P =0.0009). We propose that this locus, linked to elevated HDL-C levels, confers protection against premature CHD within an FH context.

HbA1c for the Diagnosis of Diabetes Mellitus in a Developing Country. A Position Article

An Expert Committee of the American Diabetes Association and the European Association for the Study of Diabetes recommended a move to the use of HbA1c level to diagnose diabetes mellitus. Diagnosis should be made if the A1c level is > or = 6.5%. HbA1c provides a reliable measure of chronic glycemia, correlates well with the risk of long-term diabetes complications and technical limitations for standardization have been overcome in laboratories of the U.S. and Europe. The objective of this paper is to analyze critically the advantages and disadvantages of the use of HbA1c as a diagnostic method of diabetes in a developing country. The lack of a universal threshold for the diagnosis of diabetes, the cost of the test and the absence of the standardization network in the majority of the countries are major arguments for not including HbA1c as diagnostic criteria of diabetes. HbA1c diagnostic criteria has a low sensitivity. As a result, there is a lack of agreement between the HbA1c criteria with the other diagnostic methods that lead into significant variations in the number of affected cases. In addition, sensitivity and specificity vary among ethnic groups. No study has compared the diagnostic properties of the HbA1c in Latin America. In conclusion, the logistic limitations that exist in a large proportion of developing countries and the unsolved uncertainties that exist for the definition of the A1c criterion are strong arguments against the inclusion of HbA1c among the diagnostic criteria of diabetes.

Management of the metabolic syndrome as a strategy for preventing the macrovascular complications of type 2 diabetes: controversial issues.

The metabolic syndrome is known to increase cardiovascular morbidity and precede the development of type 2 diabetes. Even before the appearance of hyperglycemia, the components of the metabolic syndrome play a crucial role in the pathogenesis of the macrovascular complications. Thus, the recognition and treatment of the metabolic syndrome may be a strategy to prevent the most likely cause of death (i.e. cardiovascular events) in cases that eventually develop type 2 diabetes. In this review, controversial issues regarding the treatment of the two main components of the metabolic syndrome (i.e dyslipidemia and arterial hypertension) are discussed. Several disparities in the current NCEP-ATPIII recommendations, when applied to patients with the metabolic syndrome, are pointed out. In population-based studies, the number of individuals with the metabolic syndrome who would need LDL cholesterol lowering treatment following these guidelines is remarkably low compared to subjects belonging to the same risk strata (10 year risk 10-20%). Subjects with the metabolic syndrome do not fall into the same risk category, resulting in differing LDL-C targets. Also, the Framingham tables underestimate the cardiovascular risk associated with the metabolic syndrome; hence fewer cases qualify for drug therapy. In addition, LDL-C underestimates the number of atherogenic particles and is therefore not the ideal target for these patients. The selection of antihypertensive medication in the metabolic syndrome is also controversial. Thus, there is sufficient evidence for a review of the current management of the metabolic syndrome as part of a strategy to prevent the macrovascular complications in type 2 diabetes.

Beta-cell adenomas without hyperinsulinemia with use of highly specific insulin radioimmunoassays: case report and review of literature.

OBJECTIVE To report a case of a proinsulin-secreting islet cell adenoma in which the diagnosis was obscured by an ultraspecific insulin assay. METHODS We describe the case of a 46-year-old woman, who presented with fasting hypoglycemia and appropriately low insulin values. RESULTS A prolonged supervised fast produced symptomatic hypoglycemia (20 mg/dL) after only 7 hours. During the entire fasting test, highly specific insulin remained at <3 mIU/L, with a median value (and interquartile range) of 0.9 (0.8 to 2.3) mIU/L, when the glucose concentration was <50 mg/dL. The serum C-peptide level remained high normal (mean +/- SD, 2.7 +/- 0.6 ng/mL; normal fasting levels, 0.8 to 3.9), and no evidence of sulfonylurea use was detected in the patients urine. Circulating proinsulin levels were persistently high (>200 pmol/L in all determinations when hypoglycemia was present; expected value, <5 pmol/L). Magnetic resonance imaging and endoscopic ultrasonography confirmed the presence of a 2.5-cm tumor in the head of the pancreas. A proinsulin-secreting islet cell tumor was diagnosed. Surgical resection of the tumor was successfully accomplished, but diabetes mellitus developed 4 months postoperatively. CONCLUSION The diagnosis of a hypoglycemia-producing pancreatic adenoma can be missed when an ultraspecific insulin assay is used. The direct measurement of proinsulin established the diagnosis in this case.

Características de los casos con dislipidemias mixtas en un estudio de población: resultados de la Encuesta Nacional de Enfermedades Crónicas

Objective. To describe the characteristics of mixed hyperlipidemia cases, using data derived from the Encuesta Nacional de Enfermedades Cronicas (Mexican National Survey of Chronic Diseases, ENEC). Material and Methods. The ENEC was conducted in 1993, in 417 Mexican cities. Blood measurements of lipids, glucose, and insulin were obtained from 2206 cases. Differences between dyslipidemia patients and non cases were obtained using analysis of variance or the chi-squared test. Results. Mixed hyperlipidemia was diagnosed in 282 subjects (12.8%). Cases were 42.7±12.6 years old. Fifty six percent were males and 46.4% had HDL cholesterol levels 21 mU/ml, were factors associated with mixed hyperlipidemia. Conclusions. Mixed hyperlipidemia is a very common condition in Mexican adults. It is more common in males older than 30 years, with additional cardiovascular risk factors. Study findings suggest that the metabolic syndrome plays a role in the pathogene

Prevention of cardiovascular disease based on lipid lowering treatment: a challenge for the Mexican health system

OBJECTIVE To estimate the percentage of Mexican adults that may require lipid-lowering treatment according to National Cholesterol Education Program-III guidelines, using data from the National Health and Nutrition Survey 2006 (ENSANut 2006). MATERIAL AND METHODS Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9 to 12 hours fast. RESULTS A cardiovascular risk equivalent was found in 13.8% and >or=2 risk factors were present in 31.5% of the population. LDL-C concentrations were above the treatment goal in 70% of the high-risk group and in 38.6% of subjects with >or=2 risk factors. Nearly 12 million Mexicans should be taught how to change their lifestyles and close to 8 million individuals require drug therapy to decrease their cardiovascular risk. CONCLUSIONS Thirty percent of Mexican adults require some form of lipid-lowering treatment (lifestyle modifications in 36.25%, drug therapy in 24.19%).