UNASSIGNED: To develop models for progression of nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) and determine if incorporating updated information improves model performance.
UNASSIGNED: Retrospective cohort study.
UNASSIGNED: Electronic health record (EHR) data from a tertiary academic center, University of California San Francisco (UCSF), and a safety-net hospital, Zuckerberg San Francisco General (ZSFG) Hospital were used to identify patients with a diagnosis of NPDR, age ≥ 18 years, a diagnosis of type 1 or 2 diabetes mellitus, ≥ 6 months of ophthalmology follow-up, and no prior diagnosis of PDR before the index date (date of first NPDR diagnosis in the EHR).
UNASSIGNED: Four survival models were developed: Cox proportional hazards, Cox with backward selection, Cox with LASSO regression and Random Survival Forest. For each model, three variable sets were compared to determine the impact of including updated clinical information: Static0 (data up to the index date), Static6m (data updated 6 months after the index date), and Dynamic (data in Static0 plus data change during the 6-month period). The UCSF data were split into 80% training and 20% testing (internal validation). The ZSFG data were used for external validation. Model performance was evaluated by the Harrell\'s concordance index (C-Index).
UNASSIGNED: Time to PDR.
UNASSIGNED: The UCSF cohort included 1130 patients and 92 (8.1%) patients progressed to PDR. The ZSFG cohort included 687 patients and 30 (4.4%) patients progressed to PDR. All models performed similarly (C-indices ∼ 0.70) in internal validation. The random survival forest with Static6m set performed best in external validation (C-index 0.76). Insurance and age were selected or ranked as highly important by all models. Other key predictors were NPDR severity, diabetic neuropathy, number of strokes, mean Hemoglobin A1c, and number of hospital admissions.
UNASSIGNED: Our models for progression of NPDR to PDR achieved acceptable predictive performance and validated well in an external setting. Updating the baseline variables with new clinical information did not consistently improve the predictive performance.
UNASSIGNED: Proprietary or commercial disclosure may be found after the references.

UNASSIGNED: Sleeve gastrectomy is the most common surgical procedure to reduce weight and treat metabolic complications in patients with moderate-to-severe obesity; however, it affects the musculoskeletal system. Dual-energy X-ray absorptiometry (DXA), which is commonly used to measure bone mineral density (BMD), may be affected by excess fat tissue around the bones, interrupting BMD measurement. Due to the strong correlation between DXA and the Hounsfield units (HU) obtained from computed tomography (CT) scans, BMD assessment using clinical abdominal CT scans has been useful. To date, there has been no report of detailed CT evaluation in patients with severe obesity after sleeve gastrectomy.
UNASSIGNED: This study investigated the effect of sleeve gastrectomy in severely obese patients on bone and psoas muscle density, and cross-sectional area using retrospective clinical CT scans.
UNASSIGNED: This was a retrospective observational study that included 86 patients (35 males and 51 females) who underwent sleeve gastrectomy between March 2012 and May 2019. Patients\' clinical data (age at the time of surgery, sex, body weight, body mass index (BMI), comorbidities, and preoperative and postoperative blood test results, HU of the lumbar spine and psoas muscle and psoas muscle mass index (PMI)) were evaluated.
UNASSIGNED: The mean age at the time of surgery was 43 years, and the body weight and BMI significantly reduced (p < 0.01) after surgery. The mean hemoglobin A1c level showed significant improvement in males and females. Serum calcium and phosphorus levels remained unchanged before and after surgery. In CT analysis, HU of the lumbar spine and psoas muscle showed no significant decrease, but PMI showed a significant decrease (p < 0.01).
UNASSIGNED: Sleeve gastrectomy could dramatically improve anthropometric measures without causing changes in serum calcium and phosphorus levels. Preoperative and postoperative abdominal CT revealed no significant difference in the bone and psoas muscle density, and the psoas muscle mass was significantly decreased after sleeve gastrectomy.

UNASSIGNED: Type 1 diabetes (T1D) is highly prevalent in Somali immigrant children and hemoglobin A1c (HbA1c) levels are elevated in this population compared to non-Hispanic Whites. Current self-management diabetes education has not been tailored to this population. We aimed to improve delivery of T1D education to Somali immigrants by developing and testing a culturally-appropriate video-based curriculum.
UNASSIGNED: This cross-sectional study involved Somali youth ≤ 19 years with T1D followed at two pediatric tertiary centers in Minnesota. Ten Somali-language T1D education videos were developed (∼60 min for total program) based on core ADA curriculum and tailored to address cultural concerns and misconceptions. A diabetes knowledge questionnaire was administered to parents of all participants and to children aged ≥12 years. Pre- and post-educational session questionnaire mean scores were compared using a paired t-test to assess knowledge improvement immediately post-video education (primary endpoint) and retention at 3 months (secondary endpoint). HbA1c was measured pre- and 6 months post education (exploratory endpoint).
UNASSIGNED: Twenty-two Somali parents of 22 children participated (mean age 12.3 ± 4 years; 36 % female), 12 children ≥12 years. Diabetes knowledge scores significantly improved immediately post-video education compared to baseline (p = 0.012). This improvement persisted 3 months later (p = 0.0008). There was no significant change in mean HbA1c from baseline at 6 months post education (9.0 ± 1.5 % vs 9.3 ± 1.9; p = 0.6).
UNASSIGNED: Culturally and linguistically tailoring diabetes education materials to African immigrants and delivering it audio-visually could improve effectiveness of diabetes education and increase knowledge and retention compared to simply translating standard diabetes education materials. The effect on HbA1c needs further study with a larger sample size.

UNASSIGNED: Efruxifermin has shown clinical efficacy in patients with non-alcoholic steatohepatitis (NASH) and F1-F3 fibrosis. The primary objective of the BALANCED Cohort C was to assess the safety and tolerability of efruxifermin in patients with compensated NASH cirrhosis.
UNASSIGNED: Patients with NASH and stage 4 fibrosis (n = 30) were randomized 2:1 to receive efruxifermin 50 mg (n = 20) or placebo (n = 10) once-weekly for 16 weeks. The primary endpoint was safety and tolerability of efruxifermin. Secondary and exploratory endpoints included evaluation of non-invasive markers of liver injury and fibrosis, glucose and lipid metabolism, and changes in histology in a subset of patients who consented to end-of-study liver biopsy.
UNASSIGNED: Efruxifermin was safe and well-tolerated; most adverse events (AEs) were grade 1 (n = 7, 23.3%) or grade 2 (n = 19, 63.3%). The most frequent AEs were gastrointestinal, including transient, mild to moderate diarrhea, and/or nausea. Significant improvements were noted in key markers of liver injury (alanine aminotransferase) and glucose and lipid metabolism. Sixteen-week treatment with efruxifermin was associated with significant reductions in non-invasive markers of fibrosis including Pro-C3 (least squares mean change from baseline [LSMCFB] -9 μg/L efruxifermin vs. -3.4 μg/L placebo; p = 0.0130) and ELF score (-0.4 efruxifermin vs. +0.4 placebo; p = 0.0036), with a trend towards reduced liver stiffness (LSMCFB -5.7 kPa efruxifermin vs. -1.1 kPa placebo; n.s.). Of 12 efruxifermin-treated patients with liver biopsy after 16 weeks, 4 (33%) achieved fibrosis improvement of at least one stage without worsening of NASH, while an additional 3 (25%) achieved resolution of NASH, compared to 0 of 5 placebo-treated patients.
UNASSIGNED: Efruxifermin appeared safe and well-tolerated with encouraging improvements in markers of liver injury, fibrosis, and glucose and lipid metabolism following 16 weeks of treatment, warranting confirmation in larger and longer term studies.
UNASSIGNED: Cirrhosis resulting from non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease, represents a major unmet medical need. Currently there are no approved drugs for the treatment of NASH. This proof-of-concept randomized, double-blind clinical trial demonstrated the potential therapeutic benefit of efruxifermin treatment compared to placebo in patients with cirrhosis due to NASH.
UNASSIGNED: NCT03976401.

UNASSIGNED: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear.
UNASSIGNED: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), insulin resistance (HOMA2 IR and IS(OGTT Cpep)), and β-cell function (C-peptide oral disposition index, oDIcoeo), were compared before and after ETI.
UNASSIGNED: Participants were a median (IQR) of 20.4 (14.1, 28.6) years old, 75 % male. Follow-up occurred 10.5 (10.0, 12.3) months after ETI initiation. BMI z-score increased from 0.3 (-0.3, 0.8) to 0.8 (0.4, 1.5), p = 0.013 between visits. No significant differences were observed in glucose tolerance, glucose area under the curve, nor fsOGTT glucose concentrations before and after ETI. Median (IQR) C-peptide index increased from 5.7 (4.1, 8.3) to 8.8 (5.5, 10.8) p = 0.013 and HOMA2 IR increased (p < 0.001), while oDIcoeo was unchanged (p = 0.67). HbA1c decreased from 5.5 % (5.5, 5.8) to 5.4 % (5.2, 5.6) (p = 0.003) while CGM variables did not change.
UNASSIGNED: BMI z-score and measures of both insulin resistance and insulin secretion increased within the first year of ETI initiation. β-cell function adjusted for insulin sensitivity (oDIcoeo) did not change.

UNASSIGNED: Genetic variants in hepatic nuclear factor 1α (HNF1A) cause maturity-onset diabetes of the young (MODY). We sought to examine whether HNF1A MODY variants also cause neonatal hypoglycemia.
UNASSIGNED: We present 3 infants with variants in HNF1A shared with their mothers. The infants experienced neonatal hypoglycemia, 2 extending beyond 1 year and the third resolving by 28 days, and all were large for gestational age (birth weights of >99th percentile). In 2 cases, genetic testing for neonatal hypoglycemia revealed pathogenic variants in HNF1A; 1 mother was previously diagnosed with HNF1A MODY, and the other\'s genetic testing and ultimate MODY diagnosis were prompted by her child\'s hypoglycemia workup. In the third case, the infant\'s persistent hypoglycemia prompted genetic testing, revealing an HNF1A variant of uncertain significance, which was then identified in the mother.
UNASSIGNED: Genetic variants causing HNF1A MODY have not been definitively linked to neonatal hypoglycemia or fetal overgrowth in utero. MODY caused by HNF1A is clinically similar to that caused by HNF4A, for which a causal relationship with neonatal hypoglycemia is more certain. Case reports have previously implicated variants in HNF1A in congenital hyperinsulinism; however, these cases have generally not been in families with MODY. The cases presented here suggest that HNF1A variants causing MODY may also cause neonatal hypoglycemia.
UNASSIGNED: Although confounding factors make the assessment of neonatal hypoglycemia challenging, these cases offer potential support for single genetic variants in HNF1A causing both MODY and neonatal hypoglycemia, with associated fetal overgrowth in utero.

UNASSIGNED: Teprotumumab, a novel treatment for thyroid eye disease (TED), which blocks the insulin-like growth factor 1 receptor, has been associated with improvement in proptosis and inflammatory ocular symptoms. In the original trials, hyperglycemia was reported in 5% to 12% of patients; however, none required hospitalization. We report a case of hyperglycemic hyperosmolar state after the first infusion of teprotumumab.
UNASSIGNED: A 56-year-old woman with Graves\' disease, severe thyroid eye disease, and prediabetes presented with polyuria, polydipsia, nausea, abdominal pain, headache, dizziness, and a fall to the emergency department 3 weeks after her first teprotumumab infusion. She was noted to have serum glucose levels of 939 mg/dL, serum bicarbonate levels of 28 meq/dL, serum osmolality of 324 mOsm/kg, and trace ketones in urine. She was treated with intravenous fluids and insulin with subsequent improvement in clinical status and biochemical profile. She was then discharged on multiple daily injections of insulin.
UNASSIGNED: Hyperglycemia is a known adverse effect of insulin-like growth factor 1 receptor inhibitors like teprotumumab. The incidence of hyperglycemia in the original trials was 5% to 12%. Most cases were mild and resolved with titration of current diabetes medications. No cases of hospitalization due to severe hyperglycemia or hyperglycemic hyperosmolar state have been reported until now.
UNASSIGNED: We intend to highlight the severity of hyperglycemia that could occur with the use of teprotumumab and the need for research to evaluate the true incidence of this condition.

UNASSIGNED: Emphysematous cystitis (EC) is a rare urinary tract infection (UTI) typically associated with severe diabetes in older women. We present a unique case of this gas-forming infection in a man with type 2 diabetes mellitus (T2DM) treated with empagliflozin. To the best of our knowledge, this is the first case report of EC associated with the use of a sodium-glucose cotransporter 2 inhibitor (SGLT2i).
UNASSIGNED: A 62-year-old man with T2DM treated with an SGLT2i developed EC. His moderately controlled T2DM was treated for over 20 years with metformin, saxagliptin/metformin, and pioglitazone to which empagliflozin was added due to his consistently elevated hemoglobin A1c level, slightly reduced estimated glomerular filtration rate, and proteinuria. Four months after initiation of the SGLT2i, he reported lower urinary tract symptoms and was found to have EC radiographically. His urine cultures were positive for Klebsiella pneumonia and was found to have asymptomatic urinary retention. He was treated conservatively, and his outcome was favorable.
UNASSIGNED: EC is commonly seen in patients with diabetes mellitus, and symptoms range from asymptomatic to severe sepsis. Most urine cultures grow Escherichia coli and K. pneumonia. The association of increased UTIs in susceptible patients with T2DM with the use of SGLT2i is yet to be determined. Most cases of EC are diagnosed radiographically and treated conservatively, although some cases require surgical intervention.
UNASSIGNED: Initially, our patient was considered a good candidate for treatment with an SGLT2i. The subsequent development of EC precluded its further use. The role of SGLT2i in patients with T2DM susceptible to UTI is controversial.

UNASSIGNED: To evaluate high-frequency (10-kHz) spinal cord stimulation (SCS) treatment in refractory painful diabetic neuropathy.
UNASSIGNED: A prospective, multicenter randomized controlled trial was conducted between Aug 28, 2017 and March 16, 2021, comparing conventional medical management (CMM) with 10-kHz SCS+CMM. The participants had hemoglobin A1c level of less than or equal to 10% and pain greater than or equal to 5 of 10 cm on visual analog scale, with painful diabetic neuropathy symptoms 12 months or more refractory to gabapentinoids and at least 1 other analgesic class. Assessments included measures of pain, neurologic function, and health-related quality of life (HRQoL) over 12 months with optional crossover at 6 months.
UNASSIGNED: The participants were randomized 1:1 to CMM (n=103) or 10-kHz SCS+CMM (n=113). At 6 months, 77 of 95 (81%) CMM group participants opted for crossover, whereas none of the 10-kHz SCS group participants did so. At 12 months, the mean pain relief from baseline among participants implanted with 10-kHz SCS was 74.3% (95% CI, 70.1-78.5), and 121 of 142 (85%) participants were treatment responders (≥50% pain relief). Treatment with 10-kHz SCS improved HRQoL, including a mean improvement in the EuroQol 5-dimensional questionnaire index score of 0.136 (95% CI, 0.104-0.169). The participants also reported significantly less pain interference with sleep, mood, and daily activities. At 12 months, 131 of 142 (92%) participants were \"satisfied\" or \"very satisfied\" with the 10-kHz SCS treatment.
UNASSIGNED: The 10-kHz SCS treatment resulted in substantial pain relief and improvement in overall HRQoL 2.5- to 4.5-fold higher than the minimal clinically important difference. The outcomes were durable over 12 months and support 10-kHz SCS treatment in patients with refractory painful diabetic neuropathy.
UNASSIGNED: clincaltrials.gov Identifier: NCT03228420.

The use of available treatments for Fabry disease (FD) (including enzyme replacement therapy [ERT]) may be restricted by their limited symptom improvement and mode of administration. Lucerastat is currently being investigated in the MODIFY study as oral substrate reduction therapy for the treatment of FD. By reducing the net globotriaosylceramide (Gb3) load in tissues, lucerastat has disease-modifying potential to improve symptoms and delay disease progression. MODIFY is a multicenter, double-blind, randomized, placebo-controlled, parallel-group Phase 3 study (ClinicalTrial.gov: NCT03425539); here we present the rationale and design of this study. Eligible adults with a genetically confirmed diagnosis of FD and FD-specific neuropathic pain entered screening. Patients were randomized (2:1) to receive either oral lucerastat twice daily or placebo for 6 months; treatment allocation was stratified according to sex and ERT treatment status. The main objectives of MODIFY are to assess the effects of lucerastat on neuropathic pain, gastrointestinal (GI) symptoms, FD biomarkers, and determine its safety and tolerability. Neuropathic pain and GI symptoms are key features of FD that have a significant impact on quality of life. Despite various tools available to assess pain and GI symptoms, there are currently limited tools available to assess neuropathic and GI symptoms in FD, validated according to health authority guidelines. Based on FDA recommendations, we undertook a patient-reported outcome (PRO) validation study, using a novel eDiary-based PRO tool to assess the validity of evaluating neuropathic pain as a primary efficacy endpoint in MODIFY. Results from the PRO validation study are included. To date, MODIFY is the largest Phase 3 clinical study conducted in patients with FD. Enrollment to MODIFY is now complete, with 118 patients randomized. Results will be presented in a separate publication. Long-term effects of lucerastat are being assessed in the ongoing open-label extension study (NCT03737214).