High-dose Insulin Research Articles

386-P: Inpatient Hypoglycemic Rate Reduction through the Implementation of Prescriber Targeted Decision Support Tools

Introduction: Hypoglycemia has been shown to increase mortality and length of hospital stay in patients with and without diabetes. The purpose of this study is to determine if the implementation of prescriber targeted decision support tools reduces the incidence of inpatient hypoglycemic events. Methods: This pre-post intervention study included adult patients who experienced an inpatient hypoglycemic event within 24 hours of insulin administration from October 2018 to December 2019. Pregnant women and patients receiving insulin infusions were excluded. Best Practice Alerts (BPAs) and banners were implemented in January 2019 to alert providers of patients at risk for hypoglycemia. Triggers for the BPAs and banners include use of sulfonylureas with reduced renal function, high weight-based basal doses, a previous episode of hypoglycemia during the admission, or concomitant use of fluoroquinolones and scheduled insulin. The primary outcome was to measure the incidence of hypoglycemia per 1000 patient days in pre- vs. post-intervention groups. Results: In total, 1186 hypoglycemic events in the pre-intervention group were compared to 5260 events in the post-intervention group. The implementation of EMR alerts significantly decreased hypoglycemia (glucose ≤ 70 mg/dL) from 22.91 events/1000 patient days to 18.27 events/1000 patient days (p<0.001). Severe hypoglycemia (glucose < 54 mg/dL) was not significantly reduced (1.65 events/1000 patient days vs. 1.79 events/1000 patient days (p=0.453)). The use of high weight-based basal insulin doses was reduced in the post-intervention patients with normal renal function, 23.0% vs. 16.7% (p<0.001), and patients with impaired renal function, 7.1% vs. 4.9% (p=0.017). Conclusion: The implementation of prescriber targeted decision support tools was successful in reducing the overall incidence of inpatient hypoglycemia. Disclosure R.Goldstein: None. J.M.Odom: None.

895-P: Effect of Long-Term Empagliflozin Therapy on Plasma Beta-Hydroxy Butyrate (ß-OHB)—Lack of Effect of Concomitant Insulin, GLP-1 Agonist, or Pioglitazone Therapy

Sodium-glucose transporter 2 (SGLT2) inhibitors are associated with increased risk of euglycemic diabetic ketoacidosis in T2DM. Possible mechanisms include increased lipolysis, elevated glucagon, and decreased plasma insulin levels. Therefore, concomitant high dose insulin as well as thiazolidinediones could potentially attenuate the rise in β-OHB because of anti-lipolytic effects. However, this has not been examined in the real-world clinical studies. We examined the effect of long-term Empagliflozin therapy on plasma β-OHB in veterans with T2DM. A retrospective chart review was performed in 43 subjects who had fasting β-OHB, C-peptide and detailed anthropometric measurements and were followed for 23 ± 2.5 months. Subjects were categorized into two groups based on fasting β-OHB concentrations (< or ≥2.8mg/dl). Eleven patients (24.4%) had high (6.03 ±1.22mg/dl) while 32 (74.6%) had normal β-OHB (1.42±0.09 mg/dL). There was no difference in age (59 ± 4 vs 62 ±2 yrs), BMI (35±1 vs 32 ±1 kg/m2), or the duration of diabetes (15 ± 3 vs 18±2 yrs) between the two groups. Subjects with higher β-OHB had higher HbA1c (8.9 ±0.7 vs 7.9 ± 0.3%, p<0.05). There was no difference in fasting C-peptide (3.2 ± 0.9 vs 3.5 ± 0.5ng/ml), total daily insulin dose (184± 43 vs 214±19 units/day), number of subjects on Pioglitazone (54 vs 35%) or GLP-1 agonist therapy (36 vs 52%) between the two groups. In conclusion, long-term therapy with Empagliflozin leads to elevated β-OHB in 25% of T2DM and it was associated with poor glycemic control. Concomitant insulin or pioglitazone therapy did not alter plasma β-OHB concentration. Disclosure L.C.Ortiz: None. J.Wortham: None. S.Pinkson: None. J.Trejo: None. A.S.Mendoza: None. X.Chen: None. D.Tripathy: None.

1521-P: Healthy, Nonobese South Asian Men Have Both Greater Peripheral and Hepatic Insulin Resistance than Chinese Men

Introduction: South Asian individuals, despite a healthy weight, are at a greater risk of type 2 diabetes mellitus than Chinese individuals. This may be secondary to higher peripheral and/or hepatic insulin resistance (IR). Using the 2-stepped hyperinsulinemic-euglycemic clamp, we examined the differences in peripheral and hepatic insulin resistance between healthy and non-obese South Asian and Chinese men. Bioimpedance analysis was performed to assess body composition. Methods: A 2-stepped hyperinsulinemic-euglycemic clamp was performed together with a “pancreatic” clamp by infusing somatostatin. A low-dose insulin (10 mU/m2/min) was infused for 2 hours, followed by high-dose insulin infusion (40 mU/m2/min) for 2 hours. Intravenous 20% glucose was infused to maintain euglycemia (blood glucose = 95-100 mg/dl) for the clamp duration. A higher M value (mg glucose per kg bodyweight per minute) during low-dose insulin infusion reflects lower hepatic IR while a higher M value during high-dose insulin infusion reflects lower peripheral IR. Results: The 2 groups (26 South Asian and 26 Chinese men) had similar age (27.3 vs 26.2 years, p = 0.338), but the South Asian group had slightly higher BMI (24.6 vs 22.9 kg/m2, p = 0.027) and body fat % (23.9 vs. 20.6%, p < 0.05). During low-dose step, the M-value was lower among South Asians compared to Chinese (0.8 ± 0.58 vs. 1.1 ± 0.55 mg/kg/min, p = 0.027). During high-dose step, the M-value was also lower among South Asians compared to Chinese (3.2 ± 2.6 vs. 5.2 ± 3.3 mg/kg/min, p = 0.015). The differences in the M-values between South Asian and Chinese individuals remained significant after correcting for body weight and fat-free mass. Conclusion: Despite a healthy weight, young South Asians have both greater hepatic and peripheral muscle IR than Chinese. Disclosure A.Y.L.Lim: None. H.Tan: None. C.Khoo: None. Funding National Medical Research Council of Singapore (MOH-CNIG19NOV-0002)

Senescent adipocytes as potential effectors of muscle cells dysfunction: An in vitro model

Recently, there has been a growing body of evidence showing a negative effect of the white adipose tissue (WAT) dysfunction on the skeletal muscle function and quality. However, little is known about the effects of senescent adipocytes on muscle cells.Therefore, to explore potential mechanisms involved in age-related loss of muscle mass and function, we performed an in vitro experiment using conditioned medium obtained from cultures of mature and aged 3 T3-L1 adipocytes, as well as from cultures of dysfunctional adipocytes exposed to oxidative stress or high insulin doses, to treat C2C12 myocytes.The results from morphological measures indicated a significant decrease in diameter and fusion index of myotubes after treatment with medium of aged or stressed adipocytes. Aged and stressed adipocytes presented different morphological characteristics as well as a different gene expression profile of proinflammatory cytokines and ROS production. In myocytes treated with different adipocytes' conditioned media, we demonstrated a significant reduction of gene expression of myogenic differentiation markers as well as a significant increase of genes involved in atrophy. Finally, a significant reduction in protein synthesis as well as a significant increase of myostatin was found in muscle cells treated with medium of aged or stressed adipocytes compared to controls.In conclusion, these preliminary results suggest that aged adipocytes could influence negatively trophism, function and regenerative capacity of myocytes by a paracrine network of signaling.

Insulin Refill Adherence among Type 2 Diabetes Mellitus Patients Attending Public Health Clinics in Perlis, Malaysia

Poor adherence to diabetes medications, particularly insulin, is still a concern. This study aimed to assess insulin refill adherence among diabetes patients attending public health clinics in Perlis before and during the COVID-19 pandemic. The underlying factors associated with insulin refill adherence were also investigated. This cross-sectional study was conducted among type 2 diabetes mellitus patients with insulin therapy from five primary health clinics in Perlis. Simple random sampling method was used to select participants from the Pharmacy Information System (PhIS) database. Adherence to insulin refill was measured by medication possession ratio before and during the COVID-19 pandemic. A general linear model was used to identify factors associated with adherence to insulin refills. A total of 426 patients were included in this study. Patients in this study were mostly Malay (94.3%) and female (63.1%). The insulin refill adherence was significantly poorer during the COVID-19 pandemic (mean=59.24, SD=28.97) than before the pandemic (mean=68.31, SD=31.27) (p<0.001). Only total daily insulin dose (adjusted β = -0.129; p=0.012) and not having hypertension (adjusted β = -7.359; p=0.043) were significantly associated with insulin refill adherence. This study highlighted that overall insulin refill adherence among patients in public health clinics in Perlis was still low, especially during the COVID-19 pandemic. Special attention should be given to patients using high total daily insulin doses and having no hypertension to improve adherence.

Efficacy and Safety of Enteral Human Recombinant Insulin to Reduce the Time to Full Enteral Feeding in Preterm Infants: A Meta-Analytical Study.

Recombinant human insulin plays an important role in the gut maturation of preterm infants. This meta-analysis was carried out to assess the efficacy and safety of enteral recombinant human insulin in decreasing the time to full enteral feeding in preterm infants. The pooling of data from four clinical trials yielded a significant decrease in the time to full enteral feeding in preterm infants under both low (Mean difference [MD] -3.43 days; 95% CI: -6.18 to -0.69 days; I2 = 48%) and high doses of insulin (MD -7.10 days; 95% CI: -10.02 to -4.18 days; I2 = 0%). These findings require confirmation by further large trials that evaluate the efficacy and safety of enteral insulin, especially at supraphysiological doses.

Effects of concurrent canine Cushing's syndrome and diabetes Mellitus on insulin requirements, trilostane dose, and survival time

Trilostane and insulin requirements and survival time of dogs with concurrent naturally-occurring Cushing's syndrome (CS) and diabetes mellitus (DM) has not been fully investigated. This retrospective study evaluated trilostane and insulin doses in dogs with concurrent CS and DM compared to dogs with only CS or DM.Additionally, a survival analysis was performed using a Kaplan-Meier survival curve. Survival time was compared through Log-rank test. Cox proportional regression method was used to screen predictor factors of death in dogs with CS, DM or concurrent CS and DM.A total of 95 dogs were included, 47 dogs had CS, 31 dogs had DM and 17 dogs had concurrent CS and DM. After long-term follow-up, dogs with concurrent CS and DM required higher final median doses of insulin than dogs with DM [0.90 (0.73–1.1) vs 0.67 (0.55–0.73) u/kg/12 h; P = 0,002]. Conversely, the median trilostane requirements in dogs with concurrent CS and DM did not differ from the median trilostane requirements of dogs with CS [1.52 (0.76–2.80) vs 1.64 (1.19–4.95) mg/kg/day; P = 0.283]. No statistical difference was found for the median survival time between dogs with CS and dogs with concurrent CS and DM (1245 vs 892 days; p = 0.152). Although, median survival time of dogs with DM was not reached, it was longer than median survival time of dogs with CS and DM (892 days; P = 0.002). In conclusion, diabetic dogs with concurrent CS need higher insulin doses and have a shorter survival time compared to diabetic dogs without CS.

Neuropathy in adolescents with type 1 diabetes: Confirmatory diagnostic tests, bedside tests, and risk factors

AimsTo estimate the prevalence of large fiber (LFN), small fiber (SFN), and autonomic neuropathy in adolescents with type 1 diabetes using confirmatory tests known from adults and to identify risk factors and bedside methods for neuropathy. MethodsSixty adolescents with type 1 diabetes (diabetes duration > five years) and 23 control subjects underwent neurological examination and confirmatory diagnostic tests for neuropathy, including nerve conduction studies, skin biopsies determining intraepidermal nerve fiber density, quantitative sudomotor axon reflex test (QSART), cardiovascular reflex tests (CARTs), and tilt table test. Possible risk factors were analyzed. Bedside tests (biothesiometry, DPNCheck®, Sudoscan, and Vagus®device) were compared with the confirmatory tests using ROC analysis. ResultsThe prevalence of neuropathies in the adolescents with diabetes (mean HbA1c 7.6% (60 mmol/mol)) was as follows: 14% confirmed/26% subclinical LFN, 2% confirmed/25% subclinical SFN, 20% abnormal QSART, 8% abnormal CARTs, and 14% orthostatic hypotension. Higher age, higher insulin dose, previous smoking, and higher triglycerides level were found to increase the relative risk for neuropathy. The bedside tests showed poor to acceptable concordance with the confirmatory tests (all, AUC ≤ 0.75). ConclusionsThe diagnostic tests confirmed the presence of neuropathy in adolescents with diabetes and underscore the importance of prevention and screening.

P3: ECMO and Calcium Channel Blocker Overdose: A Systematic Review

Introduction: The increasing indications and prevalence of extracorporeal membrane oxygenation (ECMO) are evident by the exponential increase in ECMO in the last decade. In recent literature, ECMO use has sustained patients who have intentionally or unintentionally overdosed on cardiac medications. Specifically, calcium channel blocker overdose (CCBOD) can lead to significant cardiopulmonary dysfunction and has increased in recent years. Calcium channel blockers (CCB) block L-type voltage gated calcium channels throughout the body, and overdose results in cardiac depression, vasoplegia, and hyperglycemia. Expert consensus and poison control centers both recommend treatment with calcium, high dose insulin, inotropes, and vasopressors. Our systematic review evaluated when to initiate ECMO in the CCBOD population and the mortality rate with ECMO use. Methods: An electronic literature review was conducted to identify all relevant studies for CCB use and ECMO. PRISMA guidelines for systematic review were followed. Rayyan was used as a screening tool for blinding the authors from each other, and abstracts and full texts were reviewed by three independent authors. Inclusion criteria were strictly limited to CCB ingestion without polypharmacy. A data collection tool was devised and data was independently collected by two authors prior to statistical analysis. Data points included demographics, a list of currently recommended medical treatments for CCBOD, ECMO cannulation type, and survival to hospital discharge. Results: After exclusion of duplicates, 314 abstracts were reviewed; of these 25 papers were included from 6 different countries, with the median year of the study publication 2019. From the 25 papers, 26 patients were studied with an average patient age of 32.7 years with 42% male and 58% female. Between male and female there was no significant difference in age, type of CCB taken, or days on ECMO. Average time on ECMO was 4.3 days. Venoarterial and venovenous ECMO use were 92.3% and 7.7%, respectively. Survival to hospital discharge was 84.6%. Prior to ECMO cannulation, patients received up to six medical treatments for CCBOD, with the majority receiving four to five treatments (53.8%). There was no correlation between number of therapies and days on ECMO (r=0.092, P=0.684). Conclusion: Our systematic review demonstrates that ECMO is a newly used and possibly valuable therapy for CCBOD when medical treatment fails. Most patients received aggressive medical therapies and still were unstable enough to require ECMO. Survival to discharge after ECMO for CCBOD is substantially higher than standard VV or VA ECMO uses. While medical management is still the main therapy for CCBOD, our results show that a persistently unstable patient may benefit from prompt evaluation at an ECMO center for treatment.

Tissue injury secondary to peripheral xenobiotic administration.

A 57-year-old female with a past medical history of depression was brought in by emergency medical services after intentional ingestion of 400 mg warfarin and 200 mg amlodipine 4 hours before presentation. The patient was started on treatment for calcium channel blocker overdose, including intubation for central nervous system depression, activated charcoal, intravenous calcium and glucagon, high-dose insulin with dextrose infusion, and vasopressor support. On day 2 of hospitalization, a rash was found on the left lower extremity (see Figures 1 and 2). Tissue Injury Due to Peripheral Intravenous Calcium Chloride Administration Intravenous calcium is used to treat acute hypocalcemia, severe hyperkalemia, calcium channel blocker overdose, beta-blocker overdose, and hydrofluoric acid exposure.1 Calcium chloride is preferentially administered via a central venous catheter due to its high osmolarity and its propensity to act as a vesicant.1 Calcium gluconate is preferred over calcium chloride for peripheral administration, as it is less likely to cause tissue injury if extravasation occurs. Adverse effects of both formulations include local tissue injury, skin necrosis, calcium-induced vasoconstriction, and late-onset calcifications or calcinosis cutis.1-4 Treatment for local tissue injury includes stopping the infusion and consideration of intradermal hyaluronidase around the site to diminish tissue injury.1, 4 If tissue necrosis develops, wound care, surgical debridement, and skin grafting may be considered.3 Clinicians should familiarize themselves with local tissue injury, which can be minimized by using calcium gluconate as opposed to calcium chloride when peripheral access is present.

The Case Files

The Case Files

Type 2 diabetics on high doses of insulin: what therapeutic solution?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Insulin resistance is more frequent in type 1 diabetes patients with long disease duration.

To investigate the clinical status of insulin resistance (IR) and its correlation with disease duration in patients with type 1 diabetes (T1D). Cross-sectional data from a T1D cohort were obtained (n=923). IR-related metabolic disorders including hypertension, obesity, and dyslipidemia were used as outcome variables to explore the cut-off point for estimated glucose disposal rate (eGDR) by restricted cubic spline (RCS) curve. Regression models were used for multivariate analysis of the clinical factors associated with IR. The correlation between the status of IR and diabetes duration was depicted with the RCS curve. IR-related metabolic disorders were observed in 39.4% of patients, with 9.1% meeting the criteria for metabolic syndrome. Specifically, patients with ≥10years of T1D were more likely to have IR-related metabolic disorders (54.7% vs. 36.9%, p<0.05). The presence of IR, defined as an eGDR ≤9.0mg/kg/min, was observed in 42.2% of patients. Patients with IR had a longer diabetes duration (3.5 vs. 2.7, years, p=0.003) and higher insulin dose (0.5 vs. 0.4, units per kg per day, p<0.001). Moreover, the presence of IR showed a gradual increase during 10years' disease duration and further analysis showed that diabetes duration ≥10years was a key element behind the development of IR and IR-related metabolic disorders. The status of IR is common in T1D patients, especially in those with ≥10years of disease duration. Therapies targeting balancing glycaemic control and IR are needed to decrease the future risk of cardiovascular diseases in T1D. ClinicalTrials.gov NCT03610984 (cohort study of patients with type 1 diabetes).

Prevalence of Eating Behaviors and Their Influence on Metabolic Control of Children With Type 1 Diabetes Mellitus

Background: Since a comprehensive study of eating disorders in children with type 1 diabetes in the Iranian population is necessary, this study aimed to investigate the prevalence of eating behaviors and metabolic control status of children and adolescents with diabetes mellitus. Objectives: The present cross-sectional study aim to explore the prevalence of eating behaviors and their influence on metabolic control of children with type 1 diabetes mellitus. Methods: In this cross-sectional study, all children and adolescents 6 to 12 years old with diabetes were included. First, the prevalence of eating-related behaviors in participants was assessed and recorded. Then the recorded data were statistically analyzed. Results: The Mean±SD age of the study participants was 8.92±1.925 years. One hundred children with food approach scores above 12.29 had food-approach behaviors, and 78 children with food avoidance scores above 11.85 were classified as having food avoidance behaviors. The relationships between food-approach behaviors and hemoglobin A1C (HbA1c) and insulin dose, body mass index (BMI), and lipid profile were significant (P&lt;0.05). Nevertheless, the relationship between these variables and food avoidance behaviors was not significant (P&gt;0.05). Conclusions: High BMI, high insulin dose, increased lipid levels, and high HbA1c are associated with an increased eating tendency in children. Therefore, these children should be evaluated for disordered eating behaviors.

Catastrophic ACTH-secreting pheochromocytoma: an uncommon and challenging entity with multifaceted presentation.

Cushing's syndrome due to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) by a pheochromocytoma is a challenging condition. A woman with hypertension and an anamnestic report of a 'non-secreting' left adrenal mass developed uncontrolled blood pressure (BP), hyperglycaemia and severe hypokalaemia. ACTH-dependent severe hypercortisolism was ascertained in the absence of Cushingoid features, and a psycho-organic syndrome developed. Brain imaging revealed a splenial lesion of the corpus callosum and a pituitary microadenoma. The adrenal mass displayed high uptake on both 18F-FDG PET/CT and 68Ga-DOTATOC PET/CT; urinary metanephrine levels were greatly increased. The combination of antihypertensive drugs, high-dose potassium infusion, insulin and steroidogenesis inhibitor normalized BP, metabolic parameters and cortisol levels; laparoscopic left adrenalectomy under intravenous hydrocortisone infusion was performed. On combined histology and immunohistochemistry, an ACTH-secreting pheochromocytoma was diagnosed. The patient's clinical condition improved and remission of both hypercortisolism and catecholamine hypersecretion ensued. Brain magnetic resonance imaging showed a reduction of the splenial lesion. Off-therapy BP and metabolic parameters remained normal. The patient was discharged on cortisone replacement therapy for post-surgical hypocortisolism. EAS due to pheochromocytoma displays multifaceted clinical features and requires prompt diagnosis and multidisciplinary management in order to overcome the related severe clinical derangements. A small but significant number of cases of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome are caused by ectopic ACTH secretion by neuroendocrine tumours, which is usually associated with severe hypercortisolism causing severe clinical and metabolic derangements. Ectopic ACTH secretion by a pheochromocytoma is exceedingly rare but can be life-threatening, owing to the simultaneous excess of both cortisol and catecholamines. The combination of biochemical and hormonal testing and imaging procedures is mandatory for the diagnosis of ectopic ACTH secretion, and in the presence of an adrenal mass, the possibility of an ACTH-secreting pheochromocytoma should be taken into account. Immediate-acting steroidogenesis inhibitors are required for the treatment of hypercortisolism, and catecholamine excess should also be appropriately managed before surgical removal of the tumour. A multidisciplinary approach is required for the treatment of this challenging entity.

Mixed insulin can improve control of prednisolone-induced hyperglycaemia.

Hyperglycaemia is a common side effect of prednisolone, although there are no widely accepted guidelines for the management of glucocorticoid-induced hyperglycaemia (GIH). Our institution uses mixed insulin in a pre-breakfast or pre-breakfast and pre-lunch regimen, with the rationale that this profile of insulin action matches the physiological effect of prednisolone on blood glucose levels (BGLs). Evaluate the use of the mixed insulin (NovoMix30) in a pre-breakfast or pre-breakfast and pre-lunch regimen as management for GIH in a tertiary hospital setting. We retrospectively evaluated all inpatients coprescribed prednisolone ≥7.5 mg and NovoMix30 for at least 48 hoursover a 19-month period. BGLs were evaluated with repeated-measures analysis within four time periods across the day, beginning from the day prior to NovoMix30 administration. A total of 53 patients were identified. NovoMix30 significantly reduced BGLs in the morning (mean 12.7 ± 4.5 vs. 9.2 ± 3.9 mmol/L, P < 0.001), afternoon (mean 13.6 ± 3.8 vs. 11.9 ± 3.8 mmol/L, P = 0.001) and evening (12.1 ± 3.8 vs. 10.8 ± 3.8 mmol/L, P = 0.01). With uptitration of insulin over 3 days, 43% of all BGLs were within the target range, compared with 23% on day 0 (P < 0.001). The final median dose of NovoMix30 was 0.15 (0.10-0.22) units/kg bodyweight, or 0.40 (0.23-0.69) units/mg of prednisolone, which is lower than our hospital guideline recommends. One overnight hypoglycaemic event was observed. Mixed insulin as a pre-breakfast or pre-breakfast and pre-lunch regimen can target the hyperglycaemic pattern induced by prednisolone and minimise overnight hypoglycaemia. However, higher doses of insulin than those used in our study are likely required for optimal BGL control.

Studies are needed to support optimal insulin dose titration in gestational diabetes mellitus: A systematic review

Background and aimsWe aimed to summarise the existing literature on insulin dose titration in gestation diabetes. MethodsDatabases: Medline, EMBASE, CENTRAL and CINAHL were systematically searched for trials and observational studies comparing insulin titration strategies in gestational diabetes. ResultsNo trials comparing insulin dose titration strategies were identified. Only one small (n = 111) observational study was included. In this study, patient-led daily basal insulin titration was associated with higher insulin doses, tighter glycaemic control, and lower birthweight, vs weekly clinician-led titration. ConclusionsThere is a paucity of evidence to support optimal insulin titration in gestational diabetes. Randomized trials are required.

The subtleties of insulin treatment in patients with lipodystrophy

In the treatment of Diabetes Mellitus (DM), which develops on the basis of insulin resistance in &#x0D; patients with lipodystrophy (LD) often require high doses of insulin. Traditionally in practice is to &#x0D; gradually increase the insulin doses to achieve blood glucose normalization. &#x0D; The fact that high insulin doses require a larger injection volume, which causes impairment in the &#x0D; absorption of insulin from the subcutaneous tissue to the circulation. &#x0D; In this article, we discussed the clinical approach to insulin practice in the treatment of DM in patients &#x0D; with LD and reviewed systematically the literature.

The Gengnianchun recipe attenuates insulin resistance-induced diminished ovarian reserve through inhibiting the senescence of granulosa cells.

Insulin resistance (IR) is found in patients with polycystic ovary syndrome (PCOS), but the effects and mechanisms of IR on diminished ovarian reserve (DOR) remain unclear. This study set out to investigate the effects of IR on ovarian reserve; to explore the effects of high concentrations of insulin on the function of ovarian cells in vitro; and to validate the hypothesis that the Gengnianchun recipe (GNC) helps to attenuate DOR caused by IR through reducing the senescence of granulosa cells. Estrus cycle, follicle count, and sex hormone levels were detected to evaluate ovarian function in mice with IR caused by feeding a high-fat diet (HFD). In addition, KGN cells (human granulosa cell line) were treated with high concentrations of insulin. The staining for senescence-associatedβ-galactosidase (SA-β-gal), cell cycle, and expression levels of mRNA and gene proteins related to cell aging were detected in KGN cells treated with high concentrations of insulin. Mice treated with an HFD were fed metformin, GNC, or saline solution for 6 weeks by oral gavage. HOMA-IR, the area under the curve (AUC) of the oral glucose tolerance test (OGTT), levels of fasting blood glucose (FBG), and fasting serum insulin (FINS) were examined to confirm the IR status. Then estrus cycle, follicle count, and sex hormone levels were detected to evaluate ovarian function. Expression levels of mRNA and gene proteins related to cell aging were detected in the ovarian tissue of mice in each group. The results demonstrated that IR reduced murine ovarian reserves, and high doses of insulin caused granulosa cells to senesce. There was a considerable improvement in HFD-induced IR status in the metformin (Met) and GNC treatment groups. In addition, the expression levels of aging-associated biomarkers were much lower in GNC mice than Met mice; and both the latter groups had considerably lower levels than the HFD group. Moreover, higher follicle counts in different stages and shorter diestrus in the Met or GNC groups compared to the HFD group indicated that ovarian aging could be largely reversed. This work showed that: IR impaired ovarian reserve; high concentrations of insulin induced granulosa cell aging; and GNC attenuated ovarian function through inhibiting IR-induced cell aging.

Role of a Whole Plant-Based Diet in a Patient's Journey to Healthy Living: A Case Report

Background: A plant-based diet is associated with lower cardiovascular disease and mortality incidence. This article reports a case of a post coronary artery bypass graft, morbidly obese, uncontrolled diabetic patient who was able to reduce weight, reduce blood pressure medications, and come off insulin with a strictly plant-based diet. Case report: A 61-year-old man was seen in follow-up post coronary artery bypass grafting. He had a history of hypertension, hyperlipidemia, diabetes, morbid obesity, coronary artery disease post-stenting in 2000, and heart failure preserved ejection fraction. Post-discharge, he felt tired, had gained 7 lb with hemoglobin A1c (HbA1c) 10% on high-dose insulin, and had uncontrolled hypertension on amlodipine, bumetanide, and carvedilol. He was started on a strictly plant-based diet. He was compliant on subsequent visits. At six months follow-up, he had excellent blood pressure and glucose control. He was able to come off amlodipine, bumetanide, and insulin completely. He lost 70 lb and was more active. Discussion: A plant-based diet effectively reduces obesity, diabetes, hypertension, hyperlipidemia, and heart disease. Epidemiological studies have shown lower cardiovascular and all-cause mortality with a plant-based diet. Conclusion: A whole food, plant-based diet should be recommended to prevent and control cardiovascular risk factors and overall cardiovascular morbidity and mortality.