Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies

Type 2 diabetes mellitus (T2DM) and sarcopenia (low skeletal muscle mass and function) share a bidirectional relationship. The prevalence of these diseases increases with age and they share common risk factors. Skeletal muscle fat infiltration, commonly referred to as myosteatosis, may be a major contributor to both T2DM and sarcopenia in older adults via independent effects on insulin resistance and muscle health. Many strategies to manage T2DM result in energy restriction and subsequent weight loss, and this can lead to significant declines in muscle mass in the absence of resistance exercise, which is also a first-line treatment for sarcopenia. In this review, we highlight recent evidence on established treatments and emerging therapies targeting weight loss and muscle mass and function improvements in older adults with, or at risk of, T2DM and/or sarcopenia. This includes dietary, physical activity and exercise interventions, new generation incretin-based agonists and myostatin-based antagonists, and endoscopic bariatric therapies. We also highlight how digital health technologies and health literacy interventions can increase uptake of, and adherence to, established and emerging treatments and therapies in older adults with T2DM and/or sarcopenia.

Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate

There is a strong advocacy movement for large doses of vitamin C. Some authors argue that the biological half-life for vitamin C at high plasma levels is about 30 minutes, but these reports are the subject of some controversy. NIH researchers established the current RDA based upon tests conducted 12 hours (24 half lives) after consumption. The dynamic flow model refutes the current low-dose recommendations for dietary intakes and links Pauling's mega-dose suggestions with other reported effects of massive doses of ascorbate for the treatment of disease. Although, a couple of controlled clinical studies conducted at The Mayo Clinic did not support a significant benefit for terminal cancer patients after 10 grams of once-a-day oral vitamin C, other clinical trials have demonstrated that ascorbate may indeed be effective against tumors when administered intravenously. Recent studies confirmed that plasma vitamin C concentrations vary substantially with the route of administration. Only by intravenous administration, the necessary ascorbate levels to kill cancer cells are reached in both plasma and urine. Because the efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated. One limitation of current studies is that pharmacokinetic data at high intravenous doses of vitamin C are sparse, particularly in cancer patients. This fact needs prompt attention to understand the significance of intravenous vitamin C administration. This review describes the current state-of-the-art in oral and intravenous vitamin C pharmacokinetics. In addition, the governmental recommendations of dose and frequency of vitamin C intake will also be addressed.

Secondhand smoke in the home and Pap testing among Vietnamese American women.

The purpose of this study was to report the prevalence of Vietnamese households with smokers and examine Papanicolau (Pap) testing among Vietnamese American women living in households with and without smokers. In 2002, we surveyed Vietnamese between 18 and 64 years of age from a population-based sample of randomly selected households in Seattle, Washington zip codes known to have a high density of Vietnamese residents. The response rate among eligible households was 82%, and our sample included 418 households. We used two measures of Pap testing: ever had a Pap test and had one in the last two years. Household smoking status was categorized as current smoker in the house vs. no current smoker in the house. Overall, 47% of Vietnamese American women lived with a current smoker in the household, 73% had ever received a Pap test, and 63% received one in the last two years. Pap testing behavior varied only slightly by household smoking status, and the findings were not statistically significant. With nearly half of Vietnamese women in our study currently living with smokers, future studies should examine the relationship between secondhand smoke at home and other health behaviors in Vietnamese American households.

A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients

Case studies suggest that vitamin C, given intravenously at doses of 10-100 grams/day can improve patient well being and in some cases, reduce tumor size. While ascorbate is generally considered safe, clinical data on high intravenous doses is limited. Twenty-four late stage terminal cancer patients were given continuous infusions of 150 to 710 mg/kg/day for up to eight weeks. Blood chemistry and blood count profiles were obtained at roughly one-week intervals while patient health, adverse events and tumor progression were monitored. The majority of patients were vitamin C deficient prior to treatment. Intravenous infusions increased plasma ascorbate concentrations to a mean of 1.1 mM. The most common adverse events reported were nausea, edema, and dry mouth or skin; and these were generally minor. Two Grade 3 adverse events 'possibly related' to the agent were reported: one patient with a history of renal calculi developed a kidney stone after thirteen days of treatment and another patient experienced hypokalemia after six weeks of treatment. White blood cell counts were stable while hemoglobin and hematocrit levels dropped slightly during treatment, consistent with trends observed prior to therapy. Blood creatinine, BUN, glucose, and uric acid concentrations decreased or remained stable during therapy, suggesting that ascorbate infusions did not adversely affect renal function. One patient had stable disease and continued the treatment for forty-eight weeks. These data suggest that intravenous vitamin C therapy for cancer is relatively safe, provided the patient does not have a history of kidney stone formation.

Intravenous vitamin C as a chemotherapy agent: a report on clinical cases

A series of seven cases are presented in which intravenous vitamin C has been used as antineoplastic agent in the treatment of different types of cancers. The cancers cases reviewed are the following: Renal cell carcinoma (2), Colorectal cancer (1), Pancreatic cancer (1), Non-Hodgkin's lymphoma (2) and breast cancer (1). Toxic reactions were not observed at these high doses of intravenous Vitamin C. All patients were prescreened for Glucose 6--phosphate dehydrogenase deficiency before administering intravenous Vitamin C in order to prevent hemolysis

Erythrocyte membrane fatty acid composition in cancer patients

Essential fatty acids (EFA) have an important role in complex metabolic reactions. The metabolism of essential polyunsaturated fatty acids (PUFA) appears to be one of the critical targets in the complex metabolic stages that lead to, or are associated with cancer. The goal of our research was to analyze the erythrocyte specific types of membrane fatty acid content, level and distribution in cancer patients as compared to non-cancer patients. Changes in fatty acid composition may affect different aspects of cell structure and function, including proliferation. Analyses of RBCs membrane fatty acids were performed for 255 patients with different types of cancer (breast, prostate, liver, pancreas, colon, and lung), 2,800 non-cancer patients and 34 healthy volunteers. Our research study demonstrated a lower level of stearic acid and an increased content of oleic acid in RBC of cancer patients in comparison with control and non-cancer patients. According to the results of this investigation, the ratio of Eicosa pentaenoic acid (EPA) and Decosa hexaenoic acid (DHA) to Alpha-linolenic acid (ALA) may be useful to estimate PUFA imbalances in cancer patients. EPA and DHA acid may be recommended as supplementation and in addition to current therapy during cancer treatment

Cell membrane fatty acid composition differs between normal and malignant cell lines

Twenty-eight fatty acids (C8:0 to C24:l n-9) were measured by gas chromatography in four normal cell lines (C3H / 10T1 / 2, CCD-18Co, CCD-25SK and CCD-37Lu) and seven cancer cell lines (C-41, Caov-3, LS-180, PC-3, SK-MEL-28, SK-MES-1 and U-87 MG). Results show differences in the content and proportions of fatty acids when comparing cancer cell lines with their normal counterparts. Cancer cell lines showed lower C20: 4 n-6, C24:1 n-9, polyunsaturated fatty acids (PUFA's) and ratios of C20:4 n-6 to C20:5 n-3 and C16:0 to C18:1 n-9 and stearic to oleic (SA/OA) than their normal counterparts. All cancer cell lines had SA/OA ratios lower than 7.0 while normal cell lines had ratios greater than 0.7 (p<0.05). In addition, the ratios of total saturated fatty acids (SFA) to PUFA'S and the concentration of C18:1 n-9, C18:2 n-6, C20:5 n-3 were higher in cancer cell lines as compared to normal cell lines. A positive correlation was detected between C16:0 and longer SFA'S (r = +0.511, p<0.05) in normal cell lines whereas a negative correlation (r=0.608, p<0.05) was obtained for malignant cell lines. Moreover, cancerous cell lines exhibited a particular desaturation defect and an abnormal incorporation of C18:2 n-6 and C20-4 n-6 fatty acids

Intravenous ascorbic acid: protocol for its application and use

High dose intravenous(i.v.) ascorbic acid (AA) has been used as therapy for infectious disease from bacterial and viral origin and adjuvant therapy for cancer. In this publication we describe a clinical protocol that has been developed over the past twenty years utilizing high dose i.v. AA as therapy for cancer. This includes principles of treatment, rationale, baseline workup, infusion protocol, precautions and side effects.

Disparities in access to family planning in Jamaica

In order to improve the effectiveness and subtainability of the family planning programme, the National Family Planning Board has devised a strategy to shift users to longer-acting methods and increase the role of the private sector. To design interventions, a better understanding of existing services was thought to be necessary. This study examines the distribution of family planning service delivery points in Jamaica and the services offered by the public and private sectors through an examination of records and questionnaire interviews. The study found that, because of the concentration of private sector providers - the main outlets for longer-acting methods - in urban areas, rural areas had poor access to these methods. Because rural areas are not attractive to private sector providers, the public sector should recognize the need to continue to serve these areas

The effect of user fees on the utilization of family planning services: a clinical study

A new fee structure was introduced to the Advanced Training and Research in Fertility Management Unit in 1992. The study looked at the effect of the new fees on attendance and the choice of contraceptive methods through an examination of clinic records and a questionnaire survey. There was a decline in attendance of roughly 28 per cent between 1992 and 1993. The decline affected mainly new clients and those who accepted injectables. A reduction in the price of injectables is suggested since the fee for this short-term method is more in line with those charged for long-term and permanent methods.

Serological survey for canine cutaneous and visceral leishmaniasis in areas at risk for transmission in Rio de Janeiro where prophylatic measures had been adopted

A serological survery for canine visceral (VL) and American cutaneous leishmaniasis (ACL) has been carried out during 1984-1989, to assess the effects of the prophylactic measures adopted in areas where there was a risk of transmission of the diseases in Rio de Janeiro. A previous serologival survey (1982/83) had detected serum positive dogas as well as the human disease in these same areas. A total fo 22,828 dogs have been examined in this last survey, 7,807 of which came from Campo Grande (VL and ACL area), 4,110 from Jacarepaguá (ACL area), 4,l46 from Realengo, 3,879 from Bangu and 2,886 from Senador Camará, (three VL areas). The analysis of these results showed a notable reduction in the number of serum positve dogs, compared to those of the first survey was 12.7%, against 0.62% of the second; (b) in Jacarepaguá (ACL) it decreased from 8.6%) to l.8% (c) in Bangu, Realengo and Senador Camará (VL) the rate decreased from 4.3% to 0.38%. The results indicate that this decrease was due to the prophylactic measures adopted in those areas

Non-isotopic polymerase chain reaction methods for the detection of HIV-1 in Ugandan mothers and infants

Two non-isotopic polymerase chain reaction (PCR) methods were evaluated by testing blood from 41 HIV-1-seropositive and 16 HIV-1 seronegative Ugandan mothers and 56 of their children (aged 0.5- 15.0 months). Amplification of HIV-1 sequences was performed in duplicate using a biotinylated primer pair to the gag region (SK 462-431) and nested primer pairs (JA 17-20) to the pol region of HIV-1. gag sequences were hybridized using a microtiter plate coated with the SK 102 probe followed by colorimetric detection using an avidin-horseradish peroxidase conjugate and tetramethylbenzidine/peroxide substrate. Pol sequences were detected on angarose gel stained with ethidium bromide. Results of HIV-1 PCR analysis showed that 40 out of 41 (98) seropositive mothers and 10 out of 29 (34) seropositive or Western blot-indeterminate children had detectable HIV-1 sequences. Our results suggest that non-isotopic PCR methods are sensitive; specific; and potentially useful in the early diagnosis of HIV-1 infection in developed and developing countries

Non-isotopic polymerase chain reaction methods for the detection of HIV-1 in Ugandan mothers and infants

Two non-isotopic polymerase chain reaction (PCR) methods were evaluated by testing blood from 41 HIV-1-seropositive and 16 HIV-1-seronegative Ugandan mothers and 56 of their children (aged 0.5-15.0 months). Amplification of HIV-1 sequences was performed in duplicate using a biotinylated primer pair to the gag region (SK 462-431) and nested primer pairs (JA 17-20) to the pol region of HIV-1. gag sequences were hybridized using a microtiter plate coated with the SK 102 probe followed by colorimetric detection using an avidin-horseradish peroxidase conjugate and tetramethylbenzidine/peroxide substrate. pol sequences were detected on agarose gel stained with ethidium bromide. Results of HIV-1 PCR analysis showed that 40 out of 41 (98pc) seropositive mothers and 10 out of 29 (34pc) seropositive children had detectable HIV-1 gag and pol sequences. None of the 16 seronegative mothers nor 27 seronegative or Western blot-indeterminate children had detectable HIV-1 sequences. Our results suggest that non-isotopic PCR methods are sensitive; specific; and potentially useful in the early diagnosis of HIV-1 infection in developed and developing countries