Jennifer Kyllo

Combination therapy with sitagliptin and lansoprazole in patients with recent-onset type 1 diabetes (REPAIR-T1D): 12-month results of a multicentre, randomised, placebo-controlled, phase 2 trial

Summary Background Type 1 diabetes results from autoimmune destruction of pancreatic β cells. Findings from preclinical studies suggest that dipeptidyl peptidase-4 inhibitors and proton-pump inhibitors might enhance β-cell survival and regeneration. We postulated that sitagliptin and lansoprazole would preserve β-cell function in patients with recent-onset type 1 diabetes. Methods We did a double-blind, placebo-controlled, phase 2 trial (REPAIR-T1D). Participants aged 11–36 years, diagnosed with type 1 diabetes within the past 6 months were recruited from Sanford Health Systems (Sioux Falls, SD, USA; Fargo, ND, USA), Childrens Hospitals and Clinics of Minnesota (St Paul, MN, USA), and Rady Childrens Hospital (San Diego, CA, USA). Participants were randomly assigned (2:1) to receive oral sitagliptin (100 mg for participants ≥18 years, 50 mg for those <18 years) and lansoprazole (60 mg for participants ≥18 years, 30 mg for those <18 years) or matched placebo for 12 months. Randomisation was done by a blocked randomisation process (blocks of three and six), with separate streams for younger (<18 years) and older (≥18 years) participants, and males and females. All participants and personnel remained masked until after the completion of the final 12 month visit, at which time data were unmasked to the analysis team. The primary endpoint was C-peptide response to a mixed meal challenge at 12 months measured as 2 h area under curve. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01155284. Findings Between Sept 21, 2010, and May 29, 2012, 46 participants were randomly assigned to the treatment group and 22 to the placebo group; of whom 40 participants in the treatment group and 18 in the placebo group completed the 12-month treatment. At 12 months, the mean change in C-peptide area under curve was −229 pmol/L (95% CI −316 to −142) for the treatment group and −253 pmol/L (−383 to −123) for the placebo group; this difference was not significant (p=0·77). No adverse or serious adverse events were probably or definitely related to the study treatment. Interpretation Although the expected change in the primary endpoint was not achieved, not all participants had increases in glucagon-like peptide-1 and gastrin concentrations that were expected with treatment. Although participants did not have adverse events related to study drugs, the study is not powered to address safety definitively. Further trials including these drugs might be warranted, but should be designed to ensure appropriate selection of participants and increases in these intermediary hormones. Funding Sanford Research and JDRF.

Cases of congenital adrenal hyperplasia missed by newborn screening in Minnesota

新生兒體內因缺乏21-羥化酵素(21α-hydroxylase)導致血中的 17-hydroxyprogesterone(17-OHP)濃度升高,是新生兒篩檢中鑑別先天腎上腺 增生症(CAH)的重要指標。研究基礎為明尼蘇達州自1991/1至2010/12的新生兒篩 檢共838 241例,採集新生兒出生後24-48小時篩檢血片,以時差式螢光免疫分析 法(time-resolved fluoroimmumoassay)測血片中17-OHP數值。研究方法是由明 尼蘇達州衛生部門與三家兒科內分泌中心共同合作整理新生兒篩檢結果呈偽陰 性的病例,分析包括基因檢測,血清中17-OHP數值,臨床及生化表徵。 結果: 在篩檢期間,有52例確診為典型CAH,15例典型CAH包括6例男生和9例女生 (5例salt-wasting和10例simple virilizing 型)第一次篩檢結果正常,偽陰性 率至少為22.4%。造成偽陰性結果的原因不明,可能在於17-OHP增加的時間點較 晚和/或篩檢的敏感度有關。 結論: 即使新生兒篩檢陰性也不能完全排除CAH的可能性,偽陰性結果反而會誤 導並延遲診斷。因此觀察新生兒性別特徵非常重要,尤其是女嬰性別特徵不明 時,更應該加以注意。另外,新生兒篩檢系統應加強教育臨床醫師篩檢偽陰性的 概念,對潛在的偽陰性病人加以適當的臨床關注,以便即時診斷。

Hypertension in children with congenital adrenal hyperplasia

Estimates of high blood pressure (BP) incidence in children with congenital adrenal hyperplasia (CAH) vary widely; risk factors are poorly understood. We estimated incidence of hypertension by CAH subtype and sex, and assessed its association with body mass index, hydrocortisone and fludrocortisone.

Predominance of DR3 in Somali children with type 1 diabetes in the twin cities, Minnesota

Minnesota is home to the largest Somali population in USA, and pediatric diabetes teams are seeing increasing numbers of Somali children with diabetes.

Obesity in children with congenital adrenal hyperplasia in the Minnesota cohort: importance of adjusting body mass index for height‐age

To evaluate obesity and overweight in children with congenital adrenal hyperplasia (CAH) and associations with glucocorticoids, fludrocortisone and disease control. Adjusting body mass index‐for‐height‐age (BMIHA) percentile is proposed to correct misclassification of obese/overweight status in CAH children with advanced bone age and tall‐for‐age stature.

A picture-based carbohydrate-counting resource for Somalis:

Objective Carbohydrate counting is essential for effective management of type 1 diabetes (T1D). Somali diet-specific carbohydrate-counting references are lacking, creating an additional barrier to effective diabetes control. We developed a picture-based carbohydrate-counting resource for Somalis with T1D. Methods Traditional Somali foods were selected using a variety of methods. Serving sizes and carbohydrate calculations were tabulated using the United States Department of Agriculture National Nutrient Database for Standard Reference. Carbohydrate contents of home-prepared foods were calculated by measuring the total yield and total carbohydrates of ingredients in the recipe divided by the number of servings to be consumed. When available, recipes were used for food preparation and analysis for more accurate carbohydrate estimation. Results Photographs of prepared Somali foods were compiled into a PDF file. While introductions are written in text, the resource is primarily picture-based to bypass limited literacy. The resource is shared free of charge via the following link: http://journals.sagepub.com/doi/suppl/10.1177/0300060517718732. The link will be updated annually with new information. Conclusion There is a necessity to tailor educational materials to address the needs of Somalis with diabetes. We have created a picture-based nutrition resource for carbohydrate counting of traditional Somali foods and have made this freely available to individuals worldwide.