Case presentation: A 33-year-old female presented with recurrent hypoglycemia. Endogenous hyperinsulinemia was confirmed by a prolonged fast, however serial imaging was negative. Incidental finding of an ovarian mass gave rise to the suspicion of an insulin-producing ovarian tumor. Subsequent multimodality pancreatic imaging remained negative, requiring more invasive investigations. The tumor was localized by specialized arteriography using calcium stimulation to support the diagnosis of an insulinoma. However, repeated negative imaging led to further delays in definitive management, with worsening hypoglycemia. The surgery was finally performed three years after the initial presentation with successful removal of the tumor using intra-operative ultrasound.
Clinical discussion: It is important to emphasize that preoperative radiological imaging is useful to localize pancreatic lesions. However, most insulinomas could only be detected intraoperatively. The absence of suggestive radiological evidence should not deter surgeons from proceeding with definitive surgical intervention.
Conclusion: The case highlights the importance of a multidisciplinary approach in the management of a complicated case.
Methods: This was a prospective, double-blind, randomized, placebo-controlled, clinical trial of patients with T2DM with underlying ischemic heart disease who were receiving metformin and insulin therapy (n = 81). After 12-weeks of additional therapy with either dapagliflozin (n = 40) or placebo (n = 41), systemic endothelial function was evaluated by change in flow-mediated dilation (ΔFMD), change in nitroglycerin-mediated dilation (ΔNMD) and surrogate markers including intercellular adhesion molecule 1 (ICAM-1), endothelial nitric oxide synthase (eNOS), high-sensitivity C-reactive protein (hs-CRP), and lipoprotein(a) (Lp[a]). Glycemic and lipid profiles were also measured.
Results: The dapagliflozin group demonstrated significant reductions of hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) compared to the placebo group (ΔHbA1c -0.83 ± 1.47% vs -0.16 ± 1.25%, P = 0.042 and ΔFBG vs -0.73 ± 4.55 mmol/L vs -1.90 ± 4.40 mmol/L, P = 0.015, respectively). The placebo group showed worsening of ΔFMD while the dapagliflozin group maintained similar measurements pre- and posttherapy (P = not significant). There was a reduction in ICAM-1 levels in the dapagliflozin group (-83.9 ± 205.9 ng/mL, P < 0.02), which remained unchanged in the placebo group (-11.0 ± 169.1 ng/mL, P = 0.699). Univariate correlation analysis revealed a significant negative correlation between HbA1c and ΔFMD within the active group.
Conclusion: A 12-week therapy with dapagliflozin, in addition to insulin and metformin therapies, in high-risk patients resulted in significant reductions in HbA1c, FBG, and surrogate markers of the endothelial function. Although the dapagliflozin group demonstrated a significant association between reduction in HbA1c and improvement in FMD, there was no significant difference in FMD between the 2 groups.
LEARNING POINTS: Comprehensive hormonal and radiological investigations are important in the management of a young patient with primary amenorrhoea. Coexistence pathology of two separate pathologies should be considered in patient presenting with primary amenorrhoea. Early diagnosis of MRKH or any disorders of sex development should be treated early, providing pharmacological, surgical, psychological and emotional support to the patient and reducing risk of associated complications. Abnormal pituitary hormones, particularly panhypopituitarism, would impose greater impact not only psychologically but also metabolically leading to cardiovascular, morbidity and mortality risks in this patient if not treated early. A multidisciplinary approach is necessary for patients presenting with MRKH to ensure appropriate treatments and follow-up across the lifespan of the patient.
MATERIALS AND METHODS: This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages.
RESULTS: The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p = <0.001) and improvements in body fat percentages. WC was significantly reduced in the VLCBD group, even after adjustments to age, HbA1c, weight and creatinine changes. Both dietary interventions were well received with no reported adverse events.
CONCLUSION: This study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.