Mala Dharmalingam

Background: Type 2 diabetes reversal has been viewed in the literature primarily as a dichotomous event (reversed or not reversed), even though this viewpoint may not be optimal for clinicians or patients. This cohort study’s objectives were to define stages of type 2 diabetes reversal and measure changes in reversal stages before and after 90 days of digital twin-enabled precision nutrition therapy. Methods: This study defines seven stages of diabetes reversal. The study is a retrospective pre/post comparison of changes in reversal stage, hemoglobin A1c (HbA1c), weight, body mass index (BMI), and other metrics measured before and after precision nutrition therapy. Reversal stages were defined as Stage 0: HbA1c < 5.7% without medication for > 1 year, Stage 1: HbA1c < 5.7% without medication for < 1 year, Stage 2: HbA1c < 6.5% without medication, Stage 3: estimated HbA1c (eA1c) between 5.7 and 6.4% without medication, Stage 4: estimated HbA1c (eA1c) between 5.7 and 6.4% with metformin monotherapy, Stage 5: dual oral therapy, Stage 6: > = 3 medications. Results: Reversal stage information was available for 463 patients at baseline and 90 days. At baseline, the proportions of patients in each reversal stage were Stages 1 and 2: 0%, Stage 3: 1%, Stage 4: 8%, Stage 5: 6%, and Stage 6: 85%. After 90 days, the proportions in each reversal stage were Stage 1: 2%, Stage 2: 9%, Stage 3: 32%, Stage 4: 39%, Stage 5: 7%, and Stage 6: 11%, indicating significant progress. Reversal stage progression rates varied by patient subgroup. Conclusions: Type 2 diabetes patients reached differing reversal stages during 90 days of precision nutrition therapy. Use of reversal stages may benefit patients during therapy. Trial registration: This was a retrospective study that was approved by the Medisys Clinisearch Ethical Review Board (without registration number) in 2019.

Oxidative stress is an important pathogenetic mechanism for the development of type 2 diabetes mellitus (T2DM) and its complications. Oxidative stress is an imbalance of the generation of free radicals (reactive oxygen species [ROS] and reactive nitrogen species [RNS]) and their neutralization by the antioxidant mechanisms. Increased levels of ROS and RNS lead to damage of lipids, proteins, and DNA, ultimately causing the destruction of the islet cells of pancreas through apoptosis. Another important factor in the development of diabetes mellitus and metabolic syndrome is inflammation. We studied oxidative stress in type 2 diabetic patients, patients with obesity, metabolic syndrome, and T2DM with iron-deficiency anemia. The elevation of oxidative stress in these conditions along with the increase in inflammation suggests that both oxidative stress and inflammation may heighten the risk for the development of T2DM and its complications.

Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) commonly exist together. It has been regarded as a manifestation of the metabolic syndrome. The presentations of NAFLD range from simple steatosis (NAFL), nonalcoholic steatohepatitis (NASH), and cirrhosis. NAFLD has a prevalence of 70% among T2DM patients. Overweight/obesity and insulin resistance (IR) have been strongly linked with NAFLD. Noninvasive assessment and staging of disease are based on clinical parameters such as age, sex, liver function test, platelet count, lipid profile, BMI, and imaging modalities such as USG, transient elastography (TE), and magnetic resonance imaging mass spectroscopy. Such clinical scoring systems and TE are useful in the early detection of NAFLD and predicting fibrosis. The principle behind the management of NAFLD with T2DM involves an indirect effect through improvement in IR and glycemia and thus is used for the treatment of T2DM as well.

Objectives: Glycemic excursions are commonly seen in patients admitted to the Intensive Care Unit (ICU) and are related to adverse outcomes. Glycemic gap is a marker of this excursion in patients with diabetes. It can be used to predict adverse outcomes in patients with diabetes admitted to the ICU. It is calculated by subtracting A1C-derived average glucose (ADAG) = ([28.7 × HbA1c]-46.7) from plasma glucose at admission. Objective of this study was to correlate glycemic gap and adverse outcomes in patients with type 2 diabetes mellitus (DM) admitted to the ICU. Materials and Methods: We conducted an ambispective study to include patients with type 2 DM admitted to the ICUs from July 2015 to June 2016. The following adverse outcomes were recorded: Multiorgan dysfunction syndrome (MODS), acute respiratory distress syndrome (ARDS), shock, upper gastrointestinal (UGI) bleed, acute kidney injury (AKI), and acute respiratory failure (ARF). Results: A total of 200 patients were enrolled, with a mean age ± standard deviation of 62 ± 11.24 years, and 64.5% were males. The median (interquartile range) duration of hospital stay and ICU stay were 8 (6–12) days and 4 (3–7) days, respectively. The most common primary diagnosis was cardiovascular (39.5%) followed by neurological (16.5%), infection at diagnosis (16.5%), respiratory (14%), gastrointestinal (7.5%), and others (6%). A higher glycemic gap was associated with occurrence of MODS (P < 0.01), ARDS (P = 0.026), shock (P = 0.043), UGI bleed (P = 0.013), AKI (P = 0.01), and ARF (P < 0.01). Glycemic gap cutoffs of 43.31, 45.26, and 39.12 were found to be discriminatory for predicting ICU mortality (area under the receiver operating characteristic [AUROC]=0.631, P = 0.05), MODS (AUROC = 0.725, P < 0.001), and ARF (AUROC = 0.714, P < 0.001). Conclusion: This study showed that higher glycemic gap levels were associated with an increased risk of MODS, ARDS, shock, UGI bleed, AKI, and ARF. Glycemic gap is a tool that can be used to determine prognosis in patients with diabetes admitted to the ICU.

Osteogenesis imperfecta is a common heritable connective tissue disorder. Nearly ninety percent are due to Type I collagen mutations. Type I-IV are autosomal dominant, and Type VI-XIII are autosomal recessive. They are Graded 1-5 based on severity. Genomic testing is done by collagen analysis from fibroblasts. The mainstay of treatment is bisphosphonate therapy. The prognosis is variable.