Giuseppe Bellastella

Efficacy of Insulin Analogs in Achieving the Hemoglobin A1c Target of <7% in Type 2 Diabetes: Meta-analysis of randomized controlled trials

OBJECTIVE Insulin analogs are increasingly used in patients with type 2 diabetes. We compared the effect of basal, biphasic, prandial, and basal-bolus insulin regimens with insulin analogs to reach the hemoglobin A1c (HbA1c) target of <7% in people with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted an electronic search for randomized controlled trials (RCTs) involving insulin analogs. RCTs were included if they lasted at least 12 weeks, reported the proportion of diabetic patients reaching the HbA1c target of <7% (primary outcome), and the number of patients in any arm was >30. RESULTS We found 16 RCTs, with 20 comparisons and 7,759 patients. A greater proportion of patients achieved the HbA1c goal of <7% with both biphasic (odds ratio 1.88 [95% CI 1.38–2.55]) and prandial (2.07 [1.16–3.69]) insulin compared with basal insulin; this was associated for biphasic insulin with greater hypoglycemia (event/patient/30 days, mean difference, 0.34 [range 0–0.69]) and weight gain in kg (1.0 kg [0.28–1.73]). Compared with biphasic insulin, the basal-bolus regimen was associated with a greater chance to reach the HbA1c goal (odds ratio 1.75 [95% CI 1.11–2.77]), with no greater hypoglycemia or weight gain. The effect of insulin analogs on long-term diabetes complications is still lacking. CONCLUSIONS A greater proportion of type 2 diabetic patients can achieve the HbA1c goal <7% with biphasic or prandial insulin compared with basal insulin; in absolute terms, the basal-bolus regimen was best for the attainment of the HbA1c goal.

Proportion of patients at HbA1c target <7% with eight classes of antidiabetic drugs in type 2 diabetes: systematic review of 218 randomized controlled trials with 78 945 patients

Aim: We assessed the efficacy of eight classes of diabetes medications used in current clinical practice [metformin, sulphonylureas, α‐glucosidase inhibitors, thiazolidinediones, glinides, dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide‐1 (GLP‐1) analogues and insulin analogues] to reach the HbA1c target <7% in type 2 diabetes.

Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity?

OBJECTIVE Traumatic brain injury (TBI) is a devastating public health problem that may result in hypopituitarism. However, the mechanisms responsible for hypothalamic-pituitary dysfunction due to TBI are still unclear. Although the antibodies against neurons have been demonstrated in injured animal studies, investigations regarding the occurrence of antipituitary antibodies (APAs) in patients with TBI are lacking in the literature. In order to investigate whether autoimmune mechanisms could play a role in the pituitary dysfunction after TBI, we have planned this study aimed at investigating the presence of APA at the third year of TBI and association between the TBI-induced hypopituitarism and APA. PATIENTS AND DESIGN Twenty-nine (25 males and 4 females; age 36.5+/-2.3 years) patients who had completed a 3-year follow-up after TBI were included in the present study. APA and pituitary function were evaluated in all the patients 3 years after TBI; moreover, APAs were tested also in sera of 60 age-/sex-matched normal controls. The APAs were investigated by an indirect immunofluorescence method. Results APAs were detected in 13 out of the 29 TBI patients (44.8%), but in none of the normal controls. Pituitary dysfunction development ratio was significantly higher in APA-positive patients (46.2%) when compared with APA-negative ones (12.5%; P=0.04). There was a significant association between APA positivity and hypopituitarism due to TBI (odds ratio: 2.25, 95% confidence intervals 1.1-4.6). Moreover, there was a significant positive correlation (r=0.74, P=0.004) between APA titer ratio and peak GH response to GHRH+GH related peptide (GHRP)-6 test, suggesting that high APA titers were associated with low GH response to GHRH+GHRP-6 test. CONCLUSIONS This study shows for the first time the presence of the APA in TBI patients 3 years after head trauma. Moreover, present investigation indicates preliminary evidence that APA may be associated with the development of TBI-induced pituitary dysfunction, thus suggesting that autoimmunity may contribute in the development of TBI-induced hypopituitarism. The presence of the association between APA and TBI-induced hypopituitarism may provide a new point of view in this field and promote further clinical and experimental studies.

Dipeptidyl peptidase-4 inhibitors and HbA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials

Aim: We assessed the efficacy of dipeptidyl peptidase‐4 (DPP‐4) inhibitors vildagliptin, sitagliptin, saxagliptin and alogliptin to reach the haemoglobin HbA1c target of <7% in people with type 2 diabetes.

A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses

Objectives To summarise the evidence about the efficacy of a Mediterranean diet on the management of type 2 diabetes and prediabetic states. Design A systematic review of all meta-analyses and randomised controlled trials (RCTs) that compared the Mediterranean diet with a control diet on the treatment of type 2 diabetes and prediabetic states was conducted. Electronic searches were carried out up to January 2015. Trials were included for meta-analyses if they had a control group treated with another diet, if they were of sufficient duration (at least 6 months), and if they had at least 30 participants in each arm. A random-effect model was used to pool data. Participants Adults with or at risk for type 2 diabetes. Interventions Dietary patterns that described themselves as using a ‘Mediterranean’ dietary pattern. Outcome measures The outcomes were glycaemic control, cardiovascular risk factors and remission from the metabolic syndrome. Results From 2824 studies, 8 meta-analyses and 5 RCTs were eligible. A ‘de novo’ meta-analysis of 3 long-term (>6 months) RCTs of the Mediterranean diet and glycaemic control of diabetes favoured the Mediterranean diet as compared with lower fat diets. Another ‘de novo’ meta-analysis of two long-term RCTs showed a 49% increased probability of remission from the metabolic syndrome. 5 meta-analyses showed a favourable effect of the Mediterranean diet, as compared with other diets, on body weight, total cholesterol and high-density lipoprotein cholesterol. 2 meta-analyses demonstrated that higher adherence to the Mediterranean diet reduced the risk of future diabetes by 19–23%. Conclusions The Mediterranean diet was associated with better glycaemic control and cardiovascular risk factors than control diets, including a lower fat diet, suggesting that it is suitable for the overall management of type 2 diabetes.

Diabetes and sexual dysfunction: current perspectives

Diabetes mellitus is one of the most common chronic diseases in nearly all countries. It has been associated with sexual dysfunction, both in males and in females. Diabetes is an established risk factor for sexual dysfunction in men, as a threefold increased risk of erectile dysfunction was documented in diabetic men, as compared with nondiabetic men. Among women, evidence regarding the association between diabetes and sexual dysfunction are less conclusive, although most studies have reported a higher prevalence of female sexual dysfunction in diabetic women as compared with nondiabetic women. Female sexual function appears to be more related to social and psychological components than to the physiological consequence of diabetes. Hyperglycemia, which is a main determinant of vascular and microvascular diabetic complications, may participate in the pathogenetic mechanisms of sexual dysfunction in diabetes. Moreover, diabetic people may present several clinical conditions, including hypertension, overweight and obesity, metabolic syndrome, cigarette smoking, and atherogenic dyslipidemia, which are themselves risk factors for sexual dysfunction, both in men and in women. The adoption of healthy lifestyles may reduce insulin resistance, endothelial dysfunction, and oxidative stress – all of which are desirable achievements in diabetic patients. Improved well-being may further contribute to reduce and prevent sexual dysfunction in both sexes.

Metabolic syndrome and postmenopausal breast cancer: systematic review and meta-analysis.

ObjectiveThe role of metabolic syndrome (MS) and its individual components in postmenopausal breast cancer (PBC) risk is still unclear. We reviewed and summarized epidemiological studies assessing the association of MS with the risk of PBC. MethodsWe conducted an electronic search, without restrictions, for articles published before October 31, 2012. Every included study was to report risk estimates with 95% CIs for the association between MS and PBC. Study-specific estimates were pooled using random-effects models. ResultsNine articles (with 6,417 cancer cases), all published in English, were included in the meta-analysis. MS was associated with a 52% increase in cancer risk (P < 0.001)—for the most part confined to noncohort studies (109% increased risk); the risk estimates changed little, depending on populations (United States and Europe) and definition of the syndrome (traditional vs nontraditional). The risk estimates for PBC were 1.12 (P = 0.068) for higher values of body mass index/waist circumference, 1.19 (P = 0.005) for hyperglycemia (higher fasting glucose or diabetes), 1.13 (P = 0.027) for higher blood pressure, 1.08 (P = 0.248) for higher triglycerides, and 1.39 (P = 0.008) for lower high-density lipoprotein cholesterol. All these estimates were lower than those associated with MS in the same studies. ConclusionsMS is associated with a moderately increased risk of PBC. No single component explains the risk conveyed by the full syndrome.

Investigation of antihypothalamus and antipituitary antibodies in amateur boxers: is chronic repetitive head trauma-induced pituitary dysfunction associated with autoimmunity?

OBJECTIVE Current data clearly demonstrate that sports-related chronic repetitive head trauma due to boxing might result in hypopituitarism. However, the mechanism of sports-related traumatic brain injury-induced pituitary dysfunction is still unclear. In order to understand whether autoimmune mechanisms could play a role in the pituitary dysfunction due to sports-related head trauma, we investigated the presence of antipituitary antibodies (APAs) and antihypothalamus antibodies (AHAs) in amateur boxers. PATIENTS AND DESIGN Sixty-one actively competing (n=44) or retired (n=17) male boxers (mean age, 26 years; range, 17-53) who had been evaluated regarding pituitary functions previously were included in the study. In all boxers and in 60 age/sex-similar normal controls, AHAs and APAs were investigated by an indirect immunofluorescence method. RESULTS AHAs were detected in 13 of 61 boxers (21.3%), and APAs were detected in 14 of 61 boxers (22.9%), but in none of the normal controls. Pituitary dysfunction was significantly higher in AHA-positive boxers (46.2%) than in AHA-negative boxers (10.4%) (P=0.003). There was a significant association between AHA positivity and hypopituitarism due to boxing (odds ratio: 7.37, 95% confidence interval 1.8-30.8). There was no significant association between APA positivity and hypopituitarism. CONCLUSIONS This study demonstrates for the first time the presence of AHAs and APAs in boxers who were exposed to sports-related head trauma. Moreover, the present investigation provides preliminary evidence that AHAs are associated with the development of pituitary dysfunction in boxers, thus suggesting that autoimmunity may have a role in the pathogenesis.

Anti-hypothalamus and anti-pituitary antibodies may contribute to perpetuate the hypopituitarism in patients with Sheehan's syndrome.

OBJECTIVE While anti-pituitary antibodies (APAs) were detected in some patients with Sheehans syndrome (SS) suggesting an autoimmune pituitary involvement in the development of their hypopituitarism, hypothalamic cell anti-hypothalamus antibodies (AHAs) have not been investigated so far. DESIGN The aim of this study was to evaluate the presence of AHA and APA in SS patients to verify whether an autoimmune hypothalamic-pituitary process can contribute to their late hypopituitarism. METHODS Twenty women with SS with a duration of disease ranging from 3 to 40 years (median 25.5 years) were enrolled into the study. Out of 20 patients, 12 (60%) had panhypopituitarism and the others had partial hypopituitarism well corrected with appropriate replacement therapy. None of them had clinical central diabetes insipidus. AHA and APA were investigated by immunofluorescence method in all patients. In addition, a four-layer immunofluorescence method was used to verify whether AHA immunostained vasopressin-secreting cells (AVP-c) or not. RESULTS AHAs were found in 8 out of 20 (40%) and APAs in 7 out of 20 (35%) patients with titers ranging from 1:32 to 1:128 and 1:16 to 1:32 respectively; however, in none of these positive patients AHA immunostained vasopressin cells. None of controls resulted positive for both antibodies. CONCLUSIONS Patients with SS, even many years after the onset of SS, can show antibodies to pituitary and/or hypothalamic but not AVP-secreting cells. Antibodies to unknown hypothalamic cells (releasing factor-secreting cells) other than APAs suggest that an autoimmune process involving both the hypothalamus and pituitary gland may contribute to late pituitary dysfunction in SS patients.

Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: Case Report

Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels. Magnetic resonance imaging showed olfactory bulb absence. The patient achieved virilization and spermatogenesis with gonadotrophin administration. Two years after discontinuing hormonal therapy, he maintained moderate oligozoospermia and normal testosterone levels. Prok2 and Prok-R2 gene sequence analyses were performed. The proband had a homozygous mutation in Prok-R2 exon 2 that harbours the c.T820>A base substitution, causing the introduction of an aspartic acid in place of valine at position 274 (Val274Asp). His mother had the same mutation in heterozygous state. This report describes a novel homozygous mutation of Prok-R2 gene in a man with variant KS, underlying the role of Prok-R2 gene in the olfactory and reproductive system development in humans. Present findings indicate that markedly delayed activation of gonadotrophin secretion may occur in some KS cases with definite gene defects, and that oligozoospermia might result from a variant form of reversible hypogonadotrophic hypogonadism.