Ketogenic propensity is differentially related to lipid-induced hepatic and peripheral insulin resistance.

AIM: Determine the ketogenic response (ß-hydroxybutyrate, a surrogate of hepatic ketogenesis) to a controlled lipid overload in humans. METHODS: In total, nineteen young, healthy adults (age: 28.4 ± 1.7 years; BMI: 22.7 ± 0.3 kg/m2 ) received either a 12 h overnight lipid infusion or saline in a randomized, crossover design. Plasma ketones and inflammatory markers were quantified by colorimetric and multiplex assays. Hepatic and peripheral insulin sensitivity was assessed by the hyperinsulinemic-euglycemic clamp. Skeletal muscle biopsies were obtained to quantify gene expression related to ketone body metabolism and inflammation. RESULTS: By design, the lipid overload-induced hepatic (50%, p < 0.001) and peripheral insulin resistance (73%, p < 0.01) in healthy adults. Ketones increased with hyperlipidemia and were subsequently reduced with hyperinsulinemia during the clamp procedure (Saline: Basal = 0.22 mM, Insulin = 0.07 mM; Lipid: Basal = 0.78 mM, Insulin = 0.51 mM; 2-way ANOVA: Lipid p < 0.001, Insulin p < 0.001, Interaction p = 0.07). In the saline control condition, ketones did not correlate with hepatic or peripheral insulin sensitivity. Conversely, in the lipid condition, ketones were positively correlated with hepatic insulin sensitivity (r = 0.59, p < 0.01), but inversely related to peripheral insulin sensitivity (r = -0.64, p < 0.01). Hyperlipidemia increased plasma inflammatory markers, but did not impact skeletal muscle inflammatory gene expression. Gene expression related to ketone and fatty acid metabolism in skeletal muscle increased in response to hyperlipidemia. CONCLUSION: This work provides important insight into the role of ketones in human health and suggests that ketone body metabolism is altered at the onset of lipid-induced insulin resistance.

Rationale and study design for lifestyle intervention in preparation for pregnancy (LIPP): A randomized controlled trial.

INTRODUCTION: Maternal obesity increases neonatal risk for obesity and metabolic syndrome later in life. Prior attempts to break this intergenerational obesity cycle by limiting excessive gestational weight gain have failed to reduce neonatal adiposity. Alternatively, pre-conception lifestyle interventions may improve the in utero metabolic milieu during early pregnancy leading to improved fetal outcomes. This randomized controlled trial (RCT) is evaluating whether a lifestyle intervention to reduce weight and improve maternal metabolism in preparation for pregnancy (LIPP) attenuates neonatal adiposity, compared to standard medical advice. MATERIAL AND METHODS: Overweight/class 1 obese women after a previous pregnancy, ~12 weeks postpartum, preparing for a subsequent pregnancy, will be block randomized (1:1) to either LIPP or standard of care in a parallel design. Randomization is stratified by lactation status and overweight vs. class 1 obesity. The LIPP program consists of intensive short-term weight loss followed by weight maintenance until conception using supervised exercise and a low glycemic Mediterranean diet. PRIMARY OUTCOMES: Group differences in neonatal adiposity at birth assessed by PEA POD and placental mitochondrial lipid metabolism. SECONDARY OUTCOMES: Group differences in maternal pregravid and gestational body composition, insulin sensitivity, ß-cell function, fasting metabolic and inflammatory biomarkers, and overall quality of life. Exploratory outcomes include umbilical cord blood insulin resistance, lipid profile and inflammation. DISCUSSION: This RCT will determine the efficacy of maternal weight loss prior to pregnancy on reducing neonatal adiposity. Findings may change standard obstetrical care by providing Level 1 evidence on lifestyle interventions improving neonatal outcomes for women planning for pregnancy. CLINICAL TRIAL REGISTRATION: NCT03146156.

Diabetes and technology in 2030: a utopian or dystopian future?

The ability of an individual living with diabetes to have human-to-human contact with their healthcare provider is not keeping pace with the number of people developing diabetes. From a futurist perspective, however, this dichotomy of diabetes care represents an opportunity for digital healthcare. The focus of technological innovation is unlikely to be the replacement of the multidisciplinary diabetes team but rather the provision of meaningful individual and family support between clinic visits and, on a larger scale, the facilitation of population health management for diabetes. We can also expect to see new therapies, including implantable drug delivery systems, automated closed-loop systems and miniaturized non-invasive glucose monitoring systems. New digital health technologies will create a 'digital diabetes ecosystem' to enhance rather than devolve care from humans. Concerns related to data privacy and ownership will inevitably rise, thus a future for diabetes care relying heavily on technology is not inevitably utopian. Nevertheless, revolutions in the development of novel sensors, accumulation of 'big data', and use of artificial intelligence will provide exciting opportunities for preventing, monitoring and treating diabetes in the near future.

Public health applications of Hansen's disease research and treatment.

Because of the similarities in causative agents of Hansen's disease and tuberculosis, Hansen's disease research is now being used in the identification, treatment, and prevention of tuberculosis. Numerous studies are under way to screen and develop new drugs to combat the threat of multiple drug-resistant tuberculosis. Additional studies focus on factors to reduce the transmission of tuberculosis and on the development of techniques for early diagnosis and identification of drug resistance. Advances in Hansen's disease research and treatment also are being applied to the prevention of ulcers and amputations in diabetics and others without protective sensation in their feet. The Lower Extremity Amputation Prevention Program, developed at the Gillis W. Long Hansen's Disease Center in Carville, LA, is a multidisciplinary approach that includes screening, risk assessment, and the development of a treatment plan with an emphasis on patient involvement. Expected to prevent up to 90 percent of diabetes-related amputations, the program is being implemented in Jackson, MS, in a community-based diabetic foot program and will be replicated throughout the United States.

Primary health care and the Midwest flood disaster.

The Midwest flood disaster of 1993 ravaged communities across a 9-State area. Homes were destroyed, roads closed, and services disrupted. Economic costs, including loss of revenue from farming and loss of jobs, are estimated at more than $1 billion. Even as people continue to rebuild their lives 1 year later, renewed flooding has occurred in some areas. A community-based primary health care system can be described as a system of services that (a) offers all members of a family continuous, comprehensive, quality health services throughout their lives; (b) includes case management and coordinated referrals to other related services when necessary; (c) is usually provided by family practitioners, general internists, general pediatricians, obstetricians-gynecologists, nurse practitioners, certified nurse midwives, and physician assistants; and (d) has community involvement in the development and management of the system to assure that it meets the changing needs and the diversity of the people it is designed to serve. This paper uses the floods to describe the impact of a disaster on primary health care services and primary health care systems. This includes changes in the demand for services (as evidenced by the frequency and type of patient visits) and the ability of the system to respond to these changes. The effect of a disaster on access to primary health care is discussed.

Relationship between postsurgical fibrinolytic parameters and deep vein thrombosis in surgical patients treated with compression devices.

This study consisted of 52 patients admitted for orthopedic surgery and 28 patients admitted for general surgery, who were treated with Sequential Compression Devices (SCD) and Thromboembolic Deterrent Stockings (TEDS) and monitored for the development of deep vein thrombosis (DVT). Coagulation and fibrinolytic profiles were carried out on these patients preoperatively, and on days one, three, and six postoperatively. All patients were followed by I-125-Fibrinogen scanning, Venous Doppler, and Impedance Plethysmography studies for clot detection. In the orthopedic surgery group, six (11.5%) developed DVT, and in the general surgery group, one (3.6%) developed DVT. No patients developed pulmonary embolism. The combined incidence of DVT was 8.8 per cent. A variety of parameters was measured in order to determine whether compression devices prevent a fibrinolytic shut-down commonly seen in the postsurgical patient. A combination of three assays was found to be significant in demonstrating a fibrinolytic response. These parameters were a post-surgical decrease in the plasminogen level, an increase in the level of free protease activity postoperatively, and an increase in the level of tissue plasminogen activator after surgery. 56.3 per cent of all patients treated with SCD and TEDS showed a fibrinolytic response on postoperative day one by a combination of all three of these parameters. In the group of patients that developed DVT none showed an increase in free protease activity, and five of seven showed no significant decrease in plasminogen and no increase in tissue plasminogen activator. Patients who developed thrombosis had measurable differences in their fibrinolytic system compared to those without postoperative thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Computerized call scheduling for hospital departments.

A computerized system that assigns personnel to night-call and daytime duty is described. The system reduces the department's scheduling effort from days to hours each month. It provides an equitable and unbiased assignment of staff to tasks. Information about individual qualifications and availability and about the tasks to which individuals can be assigned is entered on standard forms each month. This information is transformed into a suitable format for entering into the computer via a typewriter terminal. The computer generates a series of schedules that are printed at the terminal in a number of formats, depending upon the nature of the schedule and the type of summary requested. Equitable schedules are produced with a minimum of administrative effort. The system increases accuracy and summarizes information for control and planning.