Macrovascular complication phenotypes in type 2 diabetic patients.

BACKGROUND: Macrovascular diseases (MVD) in type 2 diabetes mellitus (T2DM) are often considered all together, without discriminating the areas involved. The aim of our study was to analyse MVD prevalence in a large population of T2DM patients by dividing the cases into subgroups according to MVD sites (NMVD, no MVD; NSCS, non-significant carotid stenosis; CBVD, cerebrovascular disease; CAD, coronary artery disease; PAD, peripheral artery disease; PVD, polyvascular disease) and studying the anthropometric, clinical and laboratory parameters in each group. METHODS: A diabetic outpatient cohort (n = 1199) was retrospectively studied. Demographic, clinical and laboratory parameters were included in analyses. A thorough cardiovascular history as documented by previous medical records (including medical and hospital records) and vascular laboratory studies (including standardised electrocardiogram, echocardiogram, provocative tests for cardiac ischaemia, ankle/brachial index, duplex ultrasonography of the carotid and lower limbs and, in selected cases, computed tomography angiography, carotid and peripheral arteriography and evaluation of transcutaneous oxygen pressure), was collected for all of the patients. Standardised procedures were used to assess microvascular complications as well as metabolic syndrome (Mets). RESULTS: The unadjusted MVD prevalence was 46.4% among the participants. The majority of patients with MVD were in the PVD group. In the multivariate analysis, age, male sex and diabetes duration were independent risk factors for PAD and PVD (P < 0.01). A low HDL-C value was an independent risk factor in the CAD and PVD groups (P = 0.03). Very high frequencies of MetS were observed in the PAD and PVD groups (94.9 and 95.7% respectively). The most MetS diagnostic criteria were recorded among members of the CAD group (all or all-1 criteria were present in 73% of patients). The average age in the CAD group (64.5 y) was comparable to that of the NMVD group. Microvascular complications were more frequent in the PAD and PVD patients. CONCLUSION: Phenotypic heterogeneity is associated with different macrovascular complications in T2DM patients. These findings might have clinical implications for developing diagnostic and therapeutic strategies targeting type 2 diabetes.

Factors that influence basal insulin requirement in type 2 diabetes.

In clinical practice, basal insulin dosage (BID) for the treatment for type 2 diabetes given as slow-acting analogues or NPH insulin varies widely when adjusted for body weight (UI/kg). In this study, we investigated the interrelationship between BID and anthropometric, laboratory and clinical parameters. A total of 681 type 2 diabetic patients, treated with bedtime insulin in association with other antidiabetic drugs (preprandial insulin and/or oral agents), were studied. Anthropometric, clinical and biochemical parameters, as well as micro- and macrovascular complications, were evaluated. Non-alcoholic fatty liver disease (NAFLD) was assessed by liver ultrasound. BID was titrated to achieve a fasting blood glucose target of ≤6.7 mmol/L (120 mg/dL). In the multivariate analysis, BID was significantly associated with waist circumference (p = 0.04) and the insulin treatment duration (p = 0.004) as the type of insulin treatment ("basal-bolus" regimen vs. basal insulin only, p < 0.0001), the use of lipid-lowering drugs (p = 0.0003) and insulin sensitizers (p = 0.005). Several glycometabolic parameters were strongly associated with BID (HbA1c p = 0.01, FPG p < 0.0001, HDL p = 0.02, triglycerides p = 0.03). Moreover, the presence of severe NAFLD resulted in a higher BID (p = 0.03). We concluded that when starting and titrating the basal insulin in type 2 diabetes, certain anthropometric, laboratory and clinical factors can be useful to find optimal BID more quickly and appropriately.

Effects of either LT4 monotherapy or LT4/LT3 combined therapy in patients totally thyroidectomized for thyroid cancer.

After total thyroidectomy all thyroid cancer patients require lifelong treatment with thyroid hormones; the treatment of choice is synthetic levothyroxine (LT4). The question of whether these patients might benefit from the combined LT4 and liothyronine (LT3) treatment has been addressed with conflicting conclusions. The aim of the present study was to compare the effects of combined low LT4/LT3 molar ratio therapy versus LT4 monotherapy on various target organs and tissues in patients thyroidectomized for thyroid cancer. Urine collection (24 hour), a fasting blood sample for laboratory examinations, thyroid function clinical score, and cardiovascular, neurological, and neuropsychological evaluations were obtained. Clinical parameters and peripheral markers of thyroid function were measured during the two different treatment regimens in 20 patients. Mean serum aspartate aminotransferase, alanine aminotransferase, sex hormone binding globulin, and osteocalcin values were significantly higher during the combined treatment. No significant differences in the clinical score, the systolic and diastolic performance, and the neurological and neuropsychological evaluations were observed between the two treatment regimens. Moreover, no alteration due to subclinical hyperthyroidism or to the fluctuations in serum T3 concentrations during the combined therapy was observed. In conclusion, we found no evidence that combined therapy with a low LT4/LT3 molar ratio resulted in improved well-being and cognitive function or in increased thyroid hormone action on peripheral tissues in respect to LT4 monotherapy. Until future large, blind, randomized, and controlled trials prove otherwise, LT4 should remain the standard treatment for thyroid cancer patients.

Thyroid hemiagenesis: prevalence in normal children and effect on thyroid function.

Thyroid hemiagenesis prevalence was studied by neck ultrasound examination in 24,032 unselected 11- to 14-yr-old schoolchildren from southeastern Sicily. Twelve cases of thyroid hemiagenesis were identified, with a prevalence of 0.05%. The female to male ratio was 1:1.4. Thyroid hemiagenesis was always due to the absence (11 cases) or severe hypoplasia (1 case) of the left lobe. The hemiagenetic thyroid volume was within the normal total thyroid volume range normalized to age in 4 of 12 cases, enlarged in 3, and significantly reduced in 5. Thyroid function (thyroid hormones and TSH, both basal and 30 min after administration of 200 micro g TRH, iv) was evaluated in 9 of 12 children and was always within the normal range. However, children with thyroid hemiagenesis had an average serum TSH significantly higher than that of 18 matched controls (2.8 +/- 0.6 vs. 1.9 +/- 0.5 mU/liter; P < 0.001). This study confirms that thyroid hemiagenesis is nearly always due to left lobe defect, and that its prevalence is similar to the cumulative prevalence of thyroid agenesis and ectopia. Compensatory hypertrophy of the residual thyroid lobe occurs in most, but not all, cases and is due to thyroid tissue overstimulation by TSH. The high risk of goiter and hypothyroidism suggests systematic follow-up of all identified cases of thyroid hemiagenesis.

Genetics of specific phenotypes of congenital hypothyroidism: a population-based approach.

Congenital hypothyroidism (CH) may cause severe and irreversible neurologic and developmental abnormalities when not recognized early. Many millions of newborns have now been screened and many thousands of patients with CH have been identified. Approximately 80%-85% have defects of thyroid gland development, while 15%-20% have congenital errors of thyroid hormone biosynthesis. An entire population screened for CH over a long period of time, was studied in the present report, using a population-based approach. In particular, two CH phenotypes, both presenting with in situ thyroid gland (patients with either goiter or with thyroid gland volume ranging from normal to hypoplasic) were analyzed. Mutations were searched in some of the most likely candidate genes: thyroperoxidase (TPO) in patients with CH goiter, Pax8 and thyrotropin receptor (TSHR) in the other group. In the former group (n = 8), four TPO gene mutations were identified in three patients. One patient was a compound heterozygous. In two cases an already described mutation (1277(insGGCC)) was present; in two other cases mutations not previously described (1996(G-->T) and 2295(G-->A)), which induced aminoacid variations with a Glu --> Stop and Val --> Ile changes, respectively, were identified. In all patients mutations were inherited from one of the parents. In the case of the compound heterozygous patient, one mutation was inherited from the mother (1277(insGGCC)) and the other from the father (1996(G-->T), Glu --> Stop). In the latter group (n = 8), a patient with a 16-base pair C(T)(13)CC deletion in TSHR gene intron 8, 42-bp distal to exon/intron 8 splice junction, was identified. No mutation was identified in Pax8 gene.