Daniela Jakubowicz

Tel Aviv University | TAU · Department of Obstetrics and Gynecology

The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not...

Obesity and diabetes are increasing worldwide in epidemic proportion. Most alarmingly, is that in the last three decades, no country has successfully succeeded in reducing obesity and diabetes rates, therefore “unless the strategies for combating this epidemic are changed,” both obesity and diabetes will increase exponentially in the years to come....

Aims Feeding regimens alter circadian rhythms in peripheral tissues, but the mechanism is not understood. We aimed to study whether soluble factors, rather than neuronal-based communication, directly influence circadian rhythms in the liver, in response to a nutritional treatment in type 2 diabetes (T2D) patients. Methods Cultured hepatocytes were...

Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of β-cell function and prevent cardiovascular complications. Most of the metabolic processes involved...

Objective: In type 2 diabetes, insulin resistance and progressive β-cell failure require treatment with high insulin doses, leading to weight gain. Our aim was to study whether a three-meal diet (3Mdiet) with a carbohydrate-rich breakfast may upregulate clock gene expression and, as a result, allow dose reduction of insulin, leading to weight loss...

Objective We examined short and long-term outcomes of bariatric surgery in patients with obesity and type 1 diabetes mellitus (T1DM). Methods We reviewed the records of all adults insured by Maccabi Healthcare Services during 2010 -2015, with body mass index (BMI) ⩾30 kg/m2 and T1DM; and compared weight reduction and glucose control according to t...

Background Diabetes mellitus (DM) is a prevalent metabolic disease characterized by chronic hyperglycemia. A primary burden of DM is related to its long-term complications, which have been shown to impact the course of hospitalization and to influence patients’ outcome. Aim To assess the role of in-hospital glucose control on length of stay, 30-da...

Objective To examine the association between hypoglycemic events and inpatient and outpatient mortality rates, and to characterize the profile of patients with diabetes who develop hypoglycemia during hospitalization in order to identify risk factors and potentially avoid it. Research design and methods This retrospective cohort study analyzed dat...

Objective: The circadian clock regulates glucose metabolism by mediating the activity of metabolic enzymes, hormones, and transport systems. Breakfast skipping and night eating have been associated with high HbA1c and postprandial hyperglycemia after lunch and dinner. Our aim was to explore the acute effect of breakfast consumption or omission on...

Background: Lifestyle weight loss interventions represent the mainstay of treating children with obesity. Long-term follow-up studies of intervention programs are scarce. This study assessed the long-term effects and identified factors associated with significant weight loss. Methods: This prospective, observational study involved 165 children w...

Acute studies show that addition of whey protein at breakfast has a glucose-lowering effect through increased incretin and insulin secretion. However, whether this is a long-term effect in type 2 diabetes is unknown. Fifty-six type 2 diabetes participants aged 58.9±4.5 yr., BMI 32.1±0.9 kg/m² and HbA1C 7.8±0.1% (61.6±0.79 mmol/mol) were randomized...

Background Diabetes is considered a major epidemic of the 21st century. Usually, diabetes begins asymptomatically and the diagnosis takes place an average of 8–12 years after the onset of dysglycaemia. Blood check for glucose is taken at different medical setting, whether at the fasting condition or randomly. Previous studies had shown that abnorma...

Background: Insulin resistance in women with polycystic ovary syndrome (PCOS) may be mediated, in part, by a deficiency in the insulin-stimulated release of a d-chiro-inositol-inositolphosphoglycan (DCI-IPG) mediator of insulin action. Supporting this idea, several studies have reported improved insulin sensitivity in both lean and obese women wit...

Aim: Dysglycemia, diabetes and abnormal blood pressure screening can be conducted by trained volunteers and may identify unknown cases. The aim of the study was to examine the feasibility and effectiveness of operating a screening station in pubic setting supervised by diabetes unit. Methods: A cross-sectional analysis of a program offering free...

Purslane extract (PE) is derived from Portulaca oleracea L., a medicinal plant used in traditional medicine for its antidiabetic properties. This randomized, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PE in improving glucose control, blood pressure, and lipid profile in adults with type 2 diabetes mellitus...

Skipping breakfast has been consistently associated with high HbA1c and postprandial hyperglycemia (PPHG) in patients with type 2 diabetes. Our aim was to explore the effect of skipping breakfast on glycemia after a subsequent isocaloric (700 kcal) lunch and dinner. In a crossover design, 22 patients with diabetes with a mean diabetes duration of 8...

Stress hyperglycaemia during hospitalisation may be the first sign of diabetes mellitus (DM). Most hospitals routinely measure blood glucose, which may enable early diagnosis. This study measured the prevalence of hyperglycaemia in hospitalised adults with no history of diabetes, and whether the discharge summary recommended work-up. Files with at...

Aims/hypothesis: High-energy breakfast and reduced-energy dinner (Bdiet) significantly reduces postprandial glycaemia in obese non-diabetic individuals. Our objective was to test whether this meal schedule reduces postprandial hyperglycaemia (PPHG) in patients with type 2 diabetes by enhancing incretin and insulin levels when compared with high-en...

Aims/hypothesis: Since protein ingestion is known to stimulate the secretion of glucagon-like peptide-1 (GLP-1), we hypothesised that enhancing GLP-1 secretion to harness its insulinotropic/beta cell-stimulating activity with whey protein pre-load may have beneficial glucose-lowering effects in type 2 diabetes. Methods: In a randomised, open-lab...

Our goal was to evaluate the effect of breakfast size and composition on body weight, glycemic control, and metabolic markers in adults with type 2 diabetes mellitus (T2DM). 59 overweight/obese adults with T2DM were randomized to one of two isocaloric diabetic diets for 3 months; big breakfast (BB), breakfast was rich in fat and protein and provide...

Objective: Few studies examined the association between time-of-day of nutrient intake and the metabolic syndrome. Our goal was to compare a weight loss diet with high caloric intake during breakfast to an isocaloric diet with high caloric intake at dinner. Design and methods: Overweight and obese women (BMI 32.4 ± 1.8 kg/m(2) ) with metabolic s...

Background: Patients with type 1 diabetes and a significant portion of patients with type 2 diabetes must use subcutaneous insulin injections, in order to maintain normoglycemia and to prevent immediate and long-term complications. For these patients, testing blood glucose levels more frequently is necessary to safely achieve glycated hemoglobin t...

In PCOS women, hyperinsulinemia stimulates ovarian cytochrome P450c17α activity that, in turn, stimulates ovarian androgen production. Our objective was to compare whether timed caloric intake differentially influences insulin resistance and hyperandrogenism in lean PCOS women. Sixty lean PCOS women (BMI 23.7±0.2kg/m2) were randomized into two isoc...

Although dietary restriction often results in initial weight loss, the majority of obese dieters fail to maintain their reduced weight. Diet-induced weight loss results in compensatory increase of hunger, craving and decreased ghrelin suppression that encourage weight regain. A high protein and carbohydrate breakfast may overcome these compensatory...

To determine whether insulin-sensitizing drugs would improve ovulation and T levels in women with polycystic ovary syndrome (PCOS), without clinical or biochemical criteria indicating insulin resistance and whether the combination of two distinct insulin-sensitizing drugs would be of any benefit over either drug alone. Randomized controlled double-...

The polycystic ovary syndrome (PCOS) is associated with an increased rate of early pregnancy loss (EPL). Hyperinsulinemia is an independent risk factor for EPL and has been found to decrease levels of glycodelin and IGF binding protein-1 (IGFBP-1), two major endometrial proteins. We hypothesized that serum glycodelin IGFBP-1 concentrations would be...

Some actions of insulin are mediated by putative inositolphosphoglycan mediators, and a deficiency in D-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) may contribute to insulin resistance in women with polycystic ovary syndrome (PCOS). Furthermore, similar effects of DCI and metformin, an insulin-sensitizing drug, have been demonstrated...

Recognition that insulin resistance plays a major role in the pathophysiology of PCOS has led to the novel application of insulin-sensitizing drugs as a treatment option for the disorder. Less appreciated, however, is the high risk for type 2 diabetes and perhaps cardiovascular disease associated with insulin resistance, and the important implicati...

To determine whether the administration of D-chiro-inositol, a putative insulin-sensitizing drug, would affect the concentration of circulating insulin, the levels of serum androgens, and the frequency of ovulation in lean women with the polycystic ovary syndrome. In 20 lean women (body mass index, 20.0 to 24.4 kg/m 2) who had the polycystic ovary...

Polycystic ovary syndrome is the most common form of female infertility in the United States. In addition to poor conception rates, pregnancy loss rates are high (30–50%) during the first trimester. We hypothesized that hyperinsulinemic insulin resistance contributes to early pregnancy loss in the syndrome, and that decreasing hyperinsulinemic insu...

Insulin resistance and its compensatory hyperinsulinemia play a key pathogenic role in the infertility of the polycystic ovary syndrome. Numerous studies indicate that insulin-sensitizing drugs can be used to enhance spontaneous ovulation and the induction of ovulation in the syndrome. The aim of this review is to summarize the studies in which ins...

We hypothesized that hyperinsulinemia contributes to early pregnancy loss in the polycystic ovary syndrome by adversely affecting endometrial function and environment. Serum glycodelin, a putative biomarker of endometrial function, is decreased in women with early pregnancy loss. Insulin-like growth factor-binding protein-1 may also play an importa...

Evidence suggests that some actions of insulin are mediated by putative inositolphosphoglycan (IPG) mediators, also known as second messengers. We review studies indicating that the IPG signaling system transduces insulin's stimulation of human thecal androgen biosynthesis, thus offering a mechanism by which insulin can stimulate ovarian androgen p...

Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a D-chiro-inositol-containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of D-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity. We measured st...

To determine whether insulin stimulates human ovarian testosterone production in the polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system, thecal cells from polycystic ovary syndrome women were isolated and cultured. Insulin and insulin-like growth factor I stimulated thecal t...

Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene. We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene. We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin o...

It is unknown whether hyperinsulinemia plays a role in the pathogenesis of polycystic ovary syndrome (PCOS) in normal weight or thin women. Evidence indicates that these women are insulin resistant and hyperinsulinemic, and this study was conducted to test the hypothesis that hyperinsulinemia stimulates ovarian cytochrome P450c17 alpha activity in...

It is unknown whether hyperinsulinemia plays a role in the pathogenesis of polycystic ovary syndrome (PCOS) in normal weight or thin women. Evidence indicates that these women are insulin resistant and hyperinsulinemic, and this study was conducted to test the hypothesis that hyperinsulinemia stimulates ovarian cytochrome P450c17 alpha activity in...

Insulin resistance and increased ovarian cytochrome P450c17 alpha activity (i.e. increased 17 alpha-hydroxylase and, to a lesser extent, increased 17,20-lyase) are both features of the polycystic ovary syndrome (PCOS). Evidence suggests that hyperinsulinemia may stimulate ovarian P450c17 alpha activity in obese women with PCOS. We hypothesized that...

Insulin resistance and increased ovarian cytochrome P450c17 alpha activity are both features of the polycystic ovary syndrome. P450c17 alpha, which is involved in androgen biosynthesis, has both 17 alpha-hydroxylase and 17,20-lyase activities. Increased activity of this enzyme results in exaggerated conversion of progesterone to 17 alpha-hydroxypro...

Dehydroepiandrosterone (DHEA) may help prevent heart disease in men. To test the hypothesis that DHEA might exert its effects by enhancing endogenous fibrinolytic potential, a double-blind, placebo-controlled study was conducted that assessed the effects of DHEA administration on plasma plasminogen activator inhibitor type 1 (PAI-1) and tissue plas...

To assess the effect of weight reduction on serum dehydroepiandrosterone (DHEA)-sulfate, insulin, and glucose, these parameters were assessed in 18 men and 29 women before and after weight loss achieved by a 2-month 1000-1400 kcal diet. Men and women did not differ at baseline with respect to age, body mass index (BMI), or serum insulin and glucose...

To assess the effect of weight reduction on serum dehydroepiandrosterone (DHEA)-sulfate, insulin, and glucose, these parameters were assessed in 18 men and 29 women before and after weight loss achieved by a 2-month 1000-1400 kcal diet. Men and women did not differ at baseline with respect to age, body mass index (BMI), or serum insulin and glucose...

To determine whether a reduction in insulinemia would be associated with a rise in serum dehydroepiandrosterone (DHEA) sulfate in insulin-resistant men, 29 middle-aged (30-59 yr old) and 28 elderly (60-80 yr old) hypertensive men were enrolled into a single blind, placebo-controlled study, in which benfluorex was administered to improve insulin sen...

To determine whether a reduction in insulinemia would be associated with a rise in serum dehydroepiandrosterone (DHEA) sulfate in insulin-resistant men, 29 middle-aged (30-59 yr old) and 28 elderly (60-80 yr old) hypertensive men were enrolled into a single blind, placebo-controlled study, in which benfluorex was administered to improve insulin sen...

Evidence suggests that amelioration of hyperinsulinemic insulin resistance in men with calcium channel blockers of the dihydropyridine class is associated with a fall in serum insulin and a rise in serum dehydroepiandrosterone sulfate (DHEA-S) concentrations. The present study was conducted to determine whether 1) the nondihydropyridine calcium cha...

Evidence suggests that amelioration of hyperinsulinemic insulin resistance in men with calcium channel blockers of the dihydropyridine class is associated with a fall in serum insulin and a rise in serum dehydroepiandrosterone sulfate (DHEA-S) concentrations. The present study was conducted to determine whether 1) the nondihydropyridine calcium cha...

Evidence suggests that hyperinsulinemic insulin resistance may reduce serum levels of the adrenal steroid dehydroepiandrosterone (DHEA) sulfate in humans. This study was conducted to assess the influence of physiological concentrations of insulin on serum adrenal steroid levels by lowering circulating insulin in nondiabetic men through the administ...

Evidence suggests that hyperinsulinemic insulin resistance may reduce serum levels of the adrenal steroid dehydroepiandrosterone (DHEA) sulfate in humans. This study was conducted to assess the influence of physiological concentrations of insulin on serum adrenal steroid levels by lowering circulating insulin in nondiabetic men through the administ...

To determine whether the calcium channel blocker amlodipine improves glucose tolerance and alters serum adrenal androgen and glucocorticoid levels in insulin-resistant men, 24 obese and hypertensive men were enrolled into a single blind, placebo-controlled study. An amlodipine group (n = 12) and a placebo group (n = 12) were studied before and afte...

To determine whether the calcium channel blocker amlodipine improves glucose tolerance and alters serum adrenal androgen and glucocorticoid levels in insulin-resistant men, 24 obese and hypertensive men were enrolled into a single blind, placebo-controlled study. An amlodipine group (n = 12) and a placebo group (n = 12) were studied before and afte...

To determine whether the calcium channel blocker nitrendipine improves glucose tolerance, lowers circulating insulin, and raises serum dehydroepiandrosterone sulfate (DHEA-S) levels in insulin-resistant men, a total of 15 obese and hypertensive men were enrolled in a single blind, placebo-controlled study. A nitrendipine group (n = 8) and a placebo...

To determine whether the calcium channel blocker nitrendipine improves glucose tolerance, lowers circulating insulin, and raises serum dehydroepiandrosterone sulfate (DHEA-S) levels in insulin-resistant men, a total of 15 obese and hypertensive men were enrolled in a single blind, placebo-controlled study. A nitrendipine group (n = 8) and a placebo...

Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE) plasma levels, cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 26 high intestinal tone (high-IT) and 24 low intestinal tone (low-IT) depressed patients, before and after the intramuscular injection of clonidine (2.5 microgr...

Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE), cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 46 normal subjects, 28 high intestinal tone (high IT) and 18 low intestinal tone (low IT), before and after the administration of a single intramuscular dose of clonidine (2....

Polycystic ovary syndrome (PCOS), a prevalent disorder in young women, is characterized by chronic anovulation and hyperandrogenism. One of the major concerns in women with PCOS has been infertility, a consequence of chronic oligo- or anovulation. However, even after ovulation is restored, either pharmacologically or via lifestyle interventions, wo...