Effects of yo-yo diet, caloric restriction, and olestra on tissue distribution of hexachlorobenzene

Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the environment and animal tissues. They enter the body in food and are stored in adipose tissue. Loss of body fat through caloric restriction mobilizes stored lipophilic xenobiotics and results in distribution to other tissues. We have studied the reversibility of this process in mice that followed a regimen of body weight cycling. Weight gain was followed by weight loss, a second gain, and a second loss ("yo-yo diet regimen"). We measured the distribution of orally gavaged [14C]hexachlorobenzene, which is sparingly metabolized. We found that weight cycling has different effects in different organs. Continued weight loss resulted in a threefold increase of 14C amount and concentration in the brain. After weight regain, 14C in the brain decreased but then increased again after a second weight loss. Weight loss resulted in an increase in the concentration of 14C in adipose tissue without changing the total amount in that tissue. Weight loss and regain resulted in an increase of 14C in the liver, which reflected an increase of fat in the liver. The regimen of weight gain and loss was repeated in mice gavaged with [14C]hexachlorobenzene, with one group receiving the nonabsorbable fat olestra in the diet. Combined dietary olestra and caloric restriction caused a 30-fold increase in the rate of excretion of 14C relative to an ad libitum diet or a reduced caloric diet alone. Distribution of 14C into the brain resulting from the restricted diet was reduced by 50% by dietary olestra.     

High-fat diet ingestion correlates with neuropathy in the duodenum myenteric plexus of obese mice with symptoms of type 2 diabetes

Obesity and type 2 diabetes are increasing in prevalence at an alarming rate in developed and developing nations and over 50 % of patients with prolonged stages of disease experience forms of autonomic neuropathy. These patients have symptoms indicating disrupted enteric nervous system function including gastric discomfort, gastroparesis and intestinal dysmotility. Previous assessments have examined enteric neuronal injury within either type 1 diabetic or transgenic type 2 diabetic context. This study aims to assess damage to myenteric neurons within the duodenum of high-fat diet ingesting mice experiencing symptoms of type 2 diabetes, as this disease context is most parallel to the human condition and disrupted duodenal motility underlies negative gastrointestinal symptoms. Mice fed a high-fat diet developed symptoms of obesity and diabetes by 4 weeks. After 8 weeks, the total number of duodenal myenteric neurons and the synaptophysin density index were reduced and transmission electron microscopy showed axonal swelling and loss of neurofilaments and microtubules, suggesting compromised neuronal health. High-fat diet ingestion correlated with a loss of neurons expressing VIP and nNOS but did not affect the expression of ChAT, substance P, calbindin and CGRP. These results correlate high-fat diet ingestion, obesity and type 2 diabetes symptoms with a loss of duodenal neurons, biasing towards those with inhibitory nature. This pathology may underlie dysmotility and other negative GI symptoms experienced by human type 2 diabetic and obese patients.     

Reduction of the body burden of PCBs and DDE by dietary intervention in a randomized trial

Serum polychlorinated biphenyls (PCBs) in Anniston, AL, residents have been associated with hypertension and diabetes. There have been no systematic interventions to reduce PCB body burdens in Anniston or other populations. Our objective was to determine the efficacy of 15 g/day of dietary olestra to reduce PCBs in Anniston residents. Blood PCBs and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene were measured at baseline and 4-month intervals in a double-blind, placebo-controlled, 1-year trial. Participants with elevated serum PCBs were randomized into two groups of 14 and received potato crisps made with olestra or vegetable oil (VO). Elimination rates during the study period were compared with 5-year prestudy rates. Eleven participants in the olestra group and 12 in the VO group completed the study. Except for one participant in the VO group, reasons for dropout were unrelated to treatments. The elimination rate of 37 non-coplanar PCB congeners during the 1-year trial was faster during olestra consumption compared to the pretrial period (−0.0829±0.0357 and −0.00864±0.0116 year⁻¹, respectively; P=.04), but not during VO consumption (−0.0413±0.0408 and −0.0283±0.0096 year⁻¹, respectively; P=.27). The concentration of PCBs in two olestra group participants decreased by 27% and 25% during the trial. There was no significant time by group interaction in change from baseline. However, group main effects for total PCBs and PCB 153 were of borderline significance. This pilot study has demonstrated that olestra can safely reduce body burdens of PCBs and supports a larger intervention trial that may also determine whether reduction in PCBs will reduce the risk of hypertension and diabetes.     

Comparison of metformin and chlorpropamide in non-obese,maturity-onset diabetics uncontrolled by diet.

The clinical effectiveness of metformin was compared with that of chlorpropamide in closely similar groups of 216 non-obese patients recently diagnosed as cases of maturity-onset diabetes that could not be controlled by diet. The incidences of primary and secondary drug failures in each group and the numbers of patients satisfactorily maintained on each of the hypoglycaemic agents throughout the first year proved remarkably similar. In 61 of the successfully treated patients who were studied by crossover to the other drug and observed for a further year the mean blood glucose concentrations at the end of the year were roughly comparable, but the mean weight response was a small loss of 1.5 +/- 3.8 kg with metformin but a gain of 4.6 +/- 3.9 kg with chlorpropamide. Thus for non-obese, maturity-onset diabetics whose disease cannot be controlled by diet and who require oral treatment sulphonylureas and biguanides are equally effective, the choice depending on whether the patient is underweight and the severity of symptoms.     

Dietary management of maturity-onset diabetes.

Dietary management of maturity-onset diabetes is a basic medical concept. It is difficult to study scientifically because of variable eating habits and the impossibility of rigorous measurement. The non-insulin-requiring diabetic patient is often managed by the family doctor, who may not have access to dietetic assistance, and assessment of the success of simple but careful dietary measures is infrequent. We have taken a special interest in this group of patients, and find that most maturity-onset diabetic patients can be satisfactorily managed on diet only. In a group of 58 such patients there was a significant fall in mean weight and fasting plasma glucose and triglyceride concentrations after six months, which persisted for up to three years. This achievement was chiefly due to those patients who were graded as "good" in their dietary adherence, but less good dieting still achieved weight loss, though plasma glucose and triglyceride concentrations did not fall so low. The clinical dietitian has played a central part in this study.     

Mucormycosis in Mato Grosso, Brazil: A Case Reports, Caused by Rhizopus microsporus var. oligosporus and Rhizopus microsporus var. rhizopodiformis

We identified the etiological agents responsible for two fatal cases of rhinocerebral mucormycosis with the classical risk factor for uncontrolled type II diabetes mellitus. Their initial symptoms did not point immediately to the suspicion of mucormycosis. Case 1, caused by Rhizopus microsporus var. oligosporus, was a 52-year-old man who presented with a painful pimple on his nose, which evolved with swelling, erythema, and a central pustule on his right hemiface suspected to be cellulitis. After 7 days of antibiotic treatment, the patient worsened with signs of sepsis and the lesion evolved to necrosis involving all his right face. Case 2, caused by Rhizopus microsporus var. rhizopodiformis, was a 57-year-old woman placed on continuous therapy with azathioprine and corticoids after a renal transplant due to chronic arterial hypertension and uncontrolled type II diabetes mellitus. Because she was suspected to have sepsis, the patient was treated with broad-spectrum antibiotics and mechanical ventilation, yet she deteriorated. Because Candida spp. were isolated from urine and a BAL, she was treated with fluconazole for 10 days, then substituted by caspofungin. Two weeks later, she presented with exophthalmus of the left eye that was surrounded by a large inflammatory and necrotic area. Both patients were the diagnosed with mucormycosis via direct microscopy of necrotic material prior to their death.     

COUNTERPOINT: Artificial Sweeteners for Obesity—Better than Sugary Alternatives; Potentially a Solution

ObjectiveNonnutritive (NNSs) are used in place of sugars to reduce caloric and glycemic intake while providing desired sweetness, commonly replacing sugar-sweetened beverages (SSBs) with “diet” (zero-calorie) alternatives. Concern has developed due to observational data associating NNSs with obesity and adiposity-based chronic disease. This counterpoint argues that, in general, NNSs used in place of added or excess sugars in the diet are likely beneficial.MethodsA literature review was conducted on interventional trials investigating NNSs and obesity or type 2 diabetes mellitus. Key words used in the search included artificial sweeteners, nonnutritive sweeteners, saccharin, sucralose, aspartame, stevia/steviol, acesulfame potassium, meal replacements, type 2 diabetes mellitus, obesity, and weight.ResultsInterventional data and indirect interventional data consistently showed beneficial effects on weight and cardiometabolic health, including glycemia, when SSBs or other energy-dense foods were replaced by artificially sweetened beverages or artificially sweetened meal replacements.ConclusionAlthough NNSs correlate with obesity and adiposity-based chronic disease, those data are fraught with confounding and error. Plausibility has been suggested on the basis of preclinical research on neuroendocrine control of appetite, satiety, and cravings plus the gut microbiome. However, interventional data reveal that replacing caloric/glycemic energy intake via NNSs creates an energy deficit resulting in weight loss and improvement in disease—especially dysglycemic disease. Intensive dietary intervention using artificially sweetened meal replacements shows a marked clinical benefit without detriment from their NNSs. Furthermore, beverages sweetened with NNSs rather than SSBs have been noted to be a critical component for those succeeding in maintaining weight loss. Although individual responses to the effects of NNSs are always warranted just like in any clinical situation, patients should not be advised to avoid NNSs in the context of dietary intervention to improve quality and energy deficit.     

Responses of gut microbiota to diet composition and weight loss in lean and obese mice

Maintenance of a reduced body weight is accompanied by a decrease in energy expenditure beyond that accounted for by reduced body mass and composition, as well as by an increased drive to eat. These effects appear to be due--in part--to reductions in circulating leptin concentrations due to loss of body fat. Gut microbiota have been implicated in the regulation of body weight. The effects of weight loss on qualitative aspects of gut microbiota have been studied in humans and mice, but these studies have been confounded by concurrent changes in diet composition, which influence microbial community composition. We studied the impact of 20% weight loss on the microbiota of diet-induced obese (DIO: 60% calories fat) mice on a high-fat diet (HFD). Weight-reduced DIO (DIO-WR) mice had the same body weight and composition as control (CON) ad-libitum (AL) fed mice being fed a control diet (10% calories fat), allowing a direct comparison of diet and weight-perturbation effects. Microbial community composition was assessed by pyrosequencing 16S rRNA genes derived from the ceca of sacrificed animals. There was a strong effect of diet composition on the diversity and composition of the microbiota. The relative abundance of specific members of the microbiota was correlated with circulating leptin concentrations and gene expression levels of inflammation markers in subcutaneous white adipose tissue in all mice. Together, these results suggest that both host adiposity and diet composition impact microbiota composition, possibly through leptin-mediated regulation of mucus production and/or inflammatory processes that alter the gut habitat.     

Degradation of olestra, a non caloric fat replacer, by microorganisms isolated from activated sludge and other environments

Olestra is a non-caloric fat substitute consisting of fatty acids esterified to sucrose. Previous work has shown that olestra is not metabolized in the gut and is excreted unmodified in human feces. To better understand the fate of olestra in engineered and natural environments, aerobic bacteria and fungi that degrade olestra were enriched from sewage sludges, soils and municipal solid waste compost not previously exposed to olestra. Various mixed and pure cultures were obtained from these sources which were able to utilize olestra as a sole carbon and energy source. The fastest growing enrichment was obtained from activated sludge and later yielded an olestra-degrading pure culture of Pseudomonas aeruginosa. This mixed culture extensively degraded both ¹⁴C-fatty acid labeled olestra and ¹⁴C-sucrose labeled olestra during 8 days of incubation. Longer-term incubation with pure cultures of P. aeruginosa demonstrated that >98% of ¹⁴C-sucrose labeled olestra and >72% of ¹⁴C-fatty acid labeled olestra was mineralized to CO₂ after 69 days. These results indicate that olestra degraders are present in environments not previously exposed to olestra and that olestra can serve as a sole carbon and energy source. Furthermore, a common bacterial species was isolated from activated sludge and shown to have the ability to degrade olestra.     

Degradation of olestra, a non caloric fat replacer, by microorganisms isolated from activated sludge and other environments

Olestra is a non-caloric fat substitute consisting of fatty acids esterified to sucrose. Previous work has shown that olestra is not metabolized in the gut and is excreted unmodified in human feces. To better understand the fate of olestra in engineered and natural environments, aerobic bacteria and fungi that degrade olestra were enriched from sewage sludges, soils and municipal solid waste compost not previously exposed to olestra. Various mixed and pure cultures were obtained from these sources which were able to utilize olestra as a sole carbon and energy source. The fastest growing enrichment was obtained from activated sludge and later yielded an olestra-degrading pure culture of Pseudomonas aeruginosa. This mixed culture extensively degraded both ¹⁴C-fatty acid labeled olestra and ¹⁴C-sucrose labeled olestra during 8 days of incubation. Longer-term incubation with pure cultures of P. aeruginosa demonstrated that >98% of ¹⁴C-sucrose labeled olestra and >72% of ¹⁴C-fatty acid labeled olestra was mineralized to CO₂ after 69 days. These results indicate that olestra degraders are present in environments not previously exposed to olestra and that olestra can serve as a sole carbon and energy source. Furthermore, a common bacterial species was isolated from activated sludge and shown to have the ability to degrade olestra.     

One-year changes in symptoms of depression and weight in overweight/obese individuals with type 2 diabetes in the Look AHEAD study

Depressed individuals are frequently excluded from weight loss trials because of fears that weight reduction may precipitate mood disorders, as well as concerns that depressed participants will not lose weight satisfactorily. The present study examined participants in the Look AHEAD study to determine whether moderate weight loss would be associated with incident symptoms of depression and suicidal ideation, and whether symptoms of depression at baseline would limit weight loss at 1 year. Overweight/obese adults with type 2 diabetes (n = 5,145) were randomly assigned to an Intensive Lifestyle Intervention (ILI) or a usual care group, Diabetes Support and Education (DSE). Of these, 5,129 participants completed the Beck Depression Inventory (BDI) and had their weight measured at baseline and 1 year. Potentially significant symptoms of depression were defined by a BDI score ≥10. Participants in ILI lost 8.6 ± 6.9% of initial weight at 1 year, compared to 0.7 ± 4.8% for DSE (P < 0.001, effect size = 1.33), and had a reduction of 1.4 ± 4.7 points on the BDI, compared to 0.4 ± 4.5 for DSE (P < 0.001, effect size = 0.23). At 1 year, the incidence of potentially significant symptoms of depression was significantly lower in the ILI than DSE group (6.3% vs. 9.6%) (relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.5, 0.8; P < 0.001). In the ILI group, participants with and without symptoms of depression lost 7.8 ± 6.7% and 8.7 ± 6.9%, respectively, a difference not considered clinically meaningful. Intentional weight loss was not associated with the precipitation of symptoms of depression, but instead appeared to protect against this occurrence. Mild (or greater) symptoms of depression at baseline did not prevent overweight/obese individuals with type 2 diabetes from achieving significant weight loss.     

The importance and effect of dietary fiber in diabetes prevention with particular consideration of whole grain products.

The state of prediabetes is characterized by an increase in insulin resistance and a decrease in pancreatic beta cell function. The prestage of type 2 diabetes mellitus can be identified by an impaired glucose tolerance and/or by an impaired fasting blood sugar. Apart from weight loss and increase in physical activity, the development of type 2 diabetes mellitus can also be prevented by dietary changes. A low-fat diet with a dietary fiber intake of more than 30g/d was shown to represent an effective preventive approach. A high-fiber diet has many positive effects on the physical health status. In addition to positive effects in the gastrointestinal tract it has an obvious potential to support weight reduction and to improve disturbances of carbohydrate and fat metabolism. At the present state of knowledge, insoluble dietary fibers as found in whole grain cereal products are considered to be especially effective in the prevention of type 2 diabetes mellitus. A high intake of fruits and vegetables as well as pulses also exerts health-promoting properties. A high-fiber diet also plays an important role in the prevention of obesity and coronary heart diseases.     

Addressing the Unmet Medical Need for Safe and Effective Weight Loss Therapies

Obesity is a significant healthcare problem worldwide and increases the risk of developing debilitating diseases including type 2 diabetes, cardiovascular disease, and cancer. Although the health benefits of weight reduction are well‐recognized, weight loss by diet and exercise fail in most patients, and the current marketed drugs have had limited success. It is clear that there is a significant unmet medical need for safe and effective weight‐reducing agents. In this review, the current status of potential weight loss approaches that are in development by the pharmaceutical and biotechnology industry are discussed. This should lead to novel treatments that can be used long‐term to effectively treat this serious metabolic disorder.     

Calcium intake and the outcome of short-term weight management

Experimental and epidemiological studies suggest that calcium intake is inversely related to weight gain. Calcium of dairy origin has been shown to be more effective in promoting weight loss. However, clinical studies yielded controversial results concerning the role of calcium intake in weight change. The aim of this study was to ascertain whether the addition of calcium can affect the outcome of 3-week weight management (WM) with a hypocaloric diet characterized by a decreased calcium intake. Overweight/ obese women (n=67; BMI 32.2+/-4.1 kg/m(2); age 49.1+/-12.1 years) underwent a 4-week comprehensive WM program. WM included a 7 MJ/day diet resulting in a stable weight during the first week and a 4.5 MJ/day diet with mean daily calcium intake 350 mg during the second to fourth week. Participants were divided into three age- and BMI-matched groups who received placebo or calcium (500 mg/day). Calcium was administered either as carbonate or calcium of dairy origin (Lactoval). There was no significant difference in weight loss in response to WM between the placebo-treated and calcium-treated groups. However, addition of calcium to the diet resulted in a lower hunger score in the Eating Inventory as well as a decrease in plasma resistin levels. Body composition measured by bioimpedance demonstrated that added calcium leads to preservation of fat-free mass. Nevertheless, a greater loss of fat-free mass in the placebo group might be partly due to a greater loss of water.     

Diabetes Disease Stage Predicts Weight Loss Outcomes with Long‐Term Appetite Suppressants

Objectives: Characterize degree of weight loss with stage of diabetes and describe its effect on cardiovascular disease risk factors in obese patients with and without diabetes. Research Methods and Procedures: Retrospective cohort analysis from patients participating in a long‐term weight management protocol using diet, exercise, behavioral modification, and appetite‐suppressant therapy. Patient groups, with (n = 19) and without diabetes (n = 19) were matched for age, gender, and weight before weight loss therapy. The effect of 12 months of therapy on weight, blood pressure, glycemic control, lipid profile, and medication requirements were tested. Additionally, patients were grouped or staged based upon therapy required for control of diabetes at the beginning of weight loss intervention. Analysis of covariance described relationships between diabetes disease stage and weight loss at 12 months. Results: Nondiabetic patients had greater mean reduction in BMI than the diabetic group (7.98 kg/m² vs. 4.77 kg/m², p < 0.01). A significant linear trend (p < 0.001) for decreasing weight loss with stage of diabetes was observed. Blood pressure, lipid profile, and glycemia improved significantly. The average daily glyburide‐equivalent dose decreased from 9.4 to 3.0 mg (p < 0.01). Discussion: Patients with diabetes lost less weight than similarly obese patients without diabetes. Regardless of differential weight loss between groups, cardiovascular disease risk factors improved. Hypoglycemic medication requirements decreased with weight loss therapy. A predictive relationship may exist between diabetes disease stage before weight loss therapy and future weight loss potential.     

Low-energy diet in atopic dermatitis patients: clinical findings and DNA damage

Undernutrition without malnutrition (low-energy diet) increases maximum longevity, reduces the incidence of several cancers and delays their onset, in animal studies. It has also been demonstrated by experimental study that caloric restriction provides a beneficial effect on various inflammatory diseases. In this study, we offered a low-energy diet to patients with atopic dermatitis (AD). Nineteen adult patients (5 males and 14 females aged 15 to 36 years) were enrolled in the study which lasted 8 weeks. The energy intake was 55% of nutritional requirements; protein was 75%, calcium 180%, iron 130%, vitamin A 105%, vitamin C 250% and vitamin E 110% of the daily requirement. No patient experienced adverse reaction, and none dropped out of the trial. Body weight, body mass index (BMI), and systolic blood pressure had decreased significantly by the end of study. The SCORAD (scoring atopic dermatitis) index, which combines objective (extent and intensity of lesions) and subjective (daytime pruritus and sleep loss) criteria, was reduced significantly. In 11 patients with severe AD, there was a significant reduction in oxidative DNA damage. The change in the inflammatory intensity score and the change in BMI caused by energy restriction showed a significant positive correlation. The change in oxidative DNA damage levels and the change in BMI showed a positive correlation. These results clarify the relationship between weight loss and the improvement of AD. It may be hypothesized that this low-energy diet which included several additional nutrients has a possibility to reduce inflammatory symptoms of patients with AD.     

Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss

Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.     

Weight Loss Reduces Liver Fat and Improves Hepatic and Skeletal Muscle Insulin Sensitivity in Obese Adolescents

Obesity in adolescents is associated with metabolic risk factors for type 2 diabetes, particularly insulin resistance and excessive accumulation of intrahepatic triglyceride (IHTG). The purpose of this study was to evaluate the effect of moderate weight loss on IHTG content and insulin sensitivity in obese adolescents who had normal oral glucose tolerance. Insulin sensitivity, assessed by using the hyperinsulinemic–euglycemic clamp technique in conjunction with stable isotopically labeled tracer infusion, and IHTG content, assessed by using magnetic resonance spectroscopy, were evaluated in eight obese adolescents (BMI ≥95th percentile for age and sex; age 15.3 ± 0.6 years) before and after moderate diet‐induced weight loss (8.2 ± 2.0% of initial body weight). Weight loss caused a 61.6 ± 8.5% decrease in IHTG content (P = 0.01), and improved both hepatic (56 ± 18% increase in hepatic insulin sensitivity index, P = 0.01) and skeletal muscle (97 ± 45% increase in insulin‐mediated glucose disposal, P = 0.01) insulin sensitivity. Moderate diet‐induced weight loss decreases IHTG content and improves insulin sensitivity in the liver and skeletal muscle in obese adolescents who have normal glucose tolerance. These results support the benefits of weight loss therapy in obese adolescents who do not have evidence of obesity‐related metabolic complications during a standard medical evaluation.     

Hyperinsulinemia Associated With Acanthosis Nigricans,Finger Pebbles,Acrochordons, And The Sign Of Leser-Trélat

ObjectiveTo review common skin manifestations associated with type 2 diabetes mellitus (DM), and to discuss a potential underlying mechanism for these manifestations.MethodsA PubMed literature search was conducted for articles describing the skin manifestations associated with hyperinsulinemia and type 2 DM. A case presentation describes a morbidly obese patient with type 2 DM treated with metformin who developed acanthosis nigricans, finger pebbles, scores of skin tags (acrochordons), and the sign of LeserTrelat (sudden onset shower of seborrheic keratoses) in the absence of internal malignancy.ResultsAcanthosis nigricans, acrochordons, and finger pebbles have been associated with type 2 DM and obesity. While the LeserTrelat sign is classically associated with internal malignancy, it can also be idiopathic. To our knowledge, this the first report of the occurrence of the LeserTrelat sign in a patient with DM absent internal malignancy.ConclusionSeveral skin manifestations can be seen in this patient with DM because of underlying insulin resistance and subsequent stimulation of insulinlike growth factor receptors. Management strategies could include weight loss, diet, and insulinsensitizing pharmacologic therapy. (Endocr Pract. 2013;19:522525)     

Aglycosuric Diabetes

The usefulness of urine tests for glucose was compared with that of blood sugar determinations in detecting diabetes mellitus in 2000 medical outpatients. Eighty-five patients proved to be diabetic, but 33 of these had no glycosuria on their first visit and would not have been detected by laboratory tests had the blood glucose levels not been measured. Exactly one-half of the new diabetics discovered would have been missed (15 of 30) had only urine tests been performed. The new diabetics who were aglycosuric at their initial examination had a mild form of the disease, were predominantly elderly, and were controlled, in nearly every case, by diet alone. Most of these patients had evidence of an elevated renal threshold for glucose. These results indicate that there is a large group of patients with mild, asymptomatic, diabetes mellitus who remain undetected unless blood tests are employed routinely. Because they have little or no glycosuria these patients do not have polydipsia, polyphagia, polyuria, or loss of weight. Automation in the medical laboratory has made routine blood tests for glucose feasible and rewarding in detecting diabetes mellitus.