The gut microbiome as possible mediator of the beneficial effects of very low calorie ketogenic diet on type 2 diabetes and obesity: a narrative review.

Several studies have shown a strong correlation between the different types of diets and gut microbiota composition on glycemia and weight loss. In this direction, low-carbohydrate and ketogenic diets have gained popularity, despite studies published so far leading to controversial results on subjects with diabetes. In this narrative review, firstly, we aimed to analyze the role of very-low-calorie ketogenic diets (VLCKDs) in type 2 diabetes (T2DM) and obesity management. Secondly, in this context, we focused attention on gut microbiota as a function of VLCKD, particularly in T2DM and obesity treatment. Finally, we reported all this evidence to underline the importance of gut microbiota to exalt new nutritional strategies for "tailor-made" management, treatment, and rehabilitation in subjects with T2DM and obesity, even with diabetic complications. In conclusion, this narrative review outlined the beneficial impact of VLCKD on gut microbiota even in subjects with T2DM and obesity, and, despite inner VLCKD short-duration feature allowing no sound-enough provisions for long-term outcomes, witnessed in favor of the short-term safety of VLCKD in those patients.Level of evidence Level V: Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Hypertensive disorders during pregnancy and 3 years after delivery in women with gestational hyperglycemia.

AIMS: Women with gestational hyperglycemia commonly experience hypertensive disorders during pregnancy. More information is needed about how hypertension develops in these patients over time. We investigated the prevalence of hypertension during and 3 years after pregnancy in Caucasian women with gestational hyperglycemia. We also investigated metabolic syndrome presence, glucose tolerance status, insulin sensitivity and insulin secretion levels in the follow-up period. METHODS: In a prospective longitudinal study with a 3-year follow-up, we assessed hypertension status and clinical-related characteristics of 103 consecutive women with gestational hyperglycemia sub-grouped according to their hypertensive status during and after pregnancy. RESULTS: Overall, 29 (28.1%) women had hypertension during pregnancy (24 gestational hypertension; 4 chronic hypertension; 1 preeclampsia). At follow-up 16 (15.5%) women were diagnosed as having hypertension (11 with hypertension in pregnancy; 5 with a normotensive pregnancy). Women with hypertension after pregnancy had higher BMI, metabolic syndrome rate and worse insulin resistance indexes than normotensive women. Weight increase at follow-up (OR 1.17, 95% CI 1.00-1.35) and hypertension in pregnancy (OR 6.72, 95% CI 1.17-38.64) were associated with hypertension after pregnancy. CONCLUSIONS: Women with gestational hyperglycemia should undergo regular monitoring during and after pregnancy to detect metabolic and clinical impairments and to prevent cardiovascular harm.

A dizygotic twin pregnancy in a MODY 3-affected woman.

BACKGROUND: MODY diabetes includes rare familiar forms due to genetic mutations resulting in ß-cell dysfunction. MODY 3 is due to mutations in the gene transcription factor HNF-1α, with diabetes diagnosis in adolescence or early adult life. Few data are available about MODY 3 in pregnancy. CASE REPORT: A 36-year-old Italian woman came to our unit at the 5th week of pregnancy. She was diagnosed with diabetes at 18 years, with negative autoimmunity and a strong familiarity for diabetes. She was treated with gliclazide and metformin. She had a previous pregnancy in which she was treated with insulin, giving birth at 38 weeks to a 3.210 kg baby girl, who showed neonatal hypoglycemia. We switched her to insulin treatment according to guidelines. We asked for genetic molecular testing, resulting in a HNF-1α gene mutation. A US examination at 7 weeks revealed a twin, bicorial, biamniotic pregnancy. At 37 weeks of gestation, she gave birth to two normal-weight baby girls; only one showed neonatal hypoglycemia and a genetic test revealed that she was affected by HNF-1α gene mutation. Subsequently, entire family of the woman was tested, showing that the father, the sister and the first daughter had the same HNF-1α mutation. DISCUSSION: A MODY 3 foetus needs a near-normal maternal glycemic control, because the exposure to intrauterine hyperglycemia can lead to an earlier age of diabetes onset. Neonatal hypoglycemia is generally observed in MODY 1 infants, but it is possible to hypothesize that some HNF-1α mutations could lead to a functionally impaired protein that might dysregulate HNF-4α expression determining hypoglycemia.

Isotretinoin treatment of autosomal recessive congenital ichthyosis complicated by coexisting dysferlinopathy.

Consanguinity is known to be associated with an increase in the prevalence of autosomal recessive disorders such as autosomal recessive congenital ichthyosis (ARCI). ARCI often responds well to retinoid treatment. We describe a patient with ARCI who improved under isotretinoin treatment. The patient subsequently developed elevated levels of serum creatinine phosphokinase (CPK), which led to the diagnosis of a second autosomal recessive disorder, dysferlinopathy, a rare myopathy characterized by muscle weakness, decreased tendon reflexes and marked elevation of CPK levels. This report demonstrates the need for physicians to remain alert to the possible coexistence of rare and mutually relevant disorders in populations with a high rate of consanguinity.

Treatment of onychomycosis: a randomized, double-blind comparison study with topical bifonazole-urea ointment alone and in combination with short-duration oral griseofulvin.

A parallel-group double-blind study was carried out which compared the efficacy of chemical avulsion of affected nail by urea 40% and bifonazole 1% cream alone with that of the same local therapy combined with short-term oral griseofulvin in onychomycosis. A total of 120 patients were included in the study. Patients' characteristics were comparable in both treatment groups. Of the 98 patients fully evaluated, 91 had toenail involvement and only seven had fingernail involvement. Forty-six of the patients were men and 51 were women. The mean age of the patients was 47.14 +/- 13.84 years (range 17-80 years). The duration of onychomycosis was for more than 1 year in 96 patients and for 3 months duration in only one patient, who was in the placebo group. Forty patients had received different previous therapies. All topical treatments were discontinued for at least 2 weeks and oral therapy for at least 2 months prior to the beginning of the study. The diagnosis was confirmed by positive mycologic cultures. Trychophyton rubrum was identified as the pathogen in 90 patients, 45 in each group, T. tonsurans in four patients, two in each group, and T. mentagrophytes in three patients, two in the griseofulvin treated group, and one in the placebo group. The first phase of treatment given to all patients consisted of occlusive dressing every 24 h with urea 40% and bifonazole 1% ointment until the infected nail became completely detached. Subsequently, in the second phase bifonazole 1% cream was applied to the nail ped every 24 h for 4 weeks. In addition, concomitantly with the bifonazole cream the patients were randomly allocated to a daily oral double-blind treatment with griseofulvin 500 mg or placebo, for 4 weeks. Clinical and mycologic evaluations were carried out at baseline, immediately after removal of the nail, and at 3 days, 4 weeks, and 4 months after the end of treatment with bifonazole cream and griseofulvin/placebo tablets. Mycologic examination included identification of fungi by KOH preparation and culture on potato dextrose agar. Positive cultures were transfered for identification on Sabouraud's. Criteria for evaluation of efficacy comprised: "cure" defined as clinical and mycologic cure (fresh specimen and culture negative) at both investigation times after the end of treatment; "late cure" defined as mycologic cure at both investigation times after the end of treatment, clinical clearing of the nail only 4 months after the end of treatment; "improvement" defined as mycologic cure and only partial clinical improvement at both times after the end of treatment; "failure" indicating no mycologic cure (fresh specimen and/or culture positive); and "relapse" signifying a change from negative findings 1 month after the end of treatment to positive findings 4 months after the end of treatment. Adverse reactions were evaluated on each visit. Only those patients who had completed clinical and mycologic evaluation during the entire study were included in the final statistical analysis. Those patients with partial evaluation were included only in the evaluation of adverse events. Based on the assumptions of a failure rate (failure and relapse) of 30% with bifonazole cream alone and of 10% with bifonazole cream and griseofulvin tables, a = 0.05 and b = 0.2 the required sample size was at least 58 patients for each treatment group (Casagrande formula, one-sided test). The primary efficacy variable "assessment of treatment" (cure and improvement versus failure and relapse) was tested for treatment differences by Fisher's exact test (a = 0.05, one-sided test; Ho, no advantage with additional systemic therapy of griseofulvin). Additionally, the relapse rates of both treatments were tested exploratively in the same way as the primary efficacy variable. All other data were analyzed descriptively.