Veikko Koivisto

Eli Lilly · Clinical Research Department

Objective. This study compared the effectiveness of Conversation Map™ (CM) education tools versus regular care of adults with type 2 diabetes. Methods. Participants from Spain and Germany were randomized to either four CM education sessions or regular care. Data were collected at baseline (visit 1), immediately post-education (visit 2), and 6 mont...

SWING was a prospective, observational study conducted in nine European countries primarily to assess direct treatment costs when switching from short-acting human insulins to rapid-acting insulin analogues (H-A) or vice versa (A-H) in patients with type 2 diabetes. Data were collected at a baseline visit (time of switch) and at approximately 3, 6...

To compare the efficacy and safety of insulin lispro protamine suspension (ILPS) versus insulin glargine once daily in a basal-bolus regimen in type 2 diabetes mellitus (T2DM) patients. Three hundred eighty-three insulin-treated patients were randomized to either ILPS plus lispro or glargine plus lispro in this open-label 24-week European study. In...

To assess the safety of the use of insulin lispro during pregnancy on the basis of published literature and to report on any related efficacy findings. The National Center for Biotechnology Information Entrez Database PubMed (http://www.ncbi. nlm.nih.gov/pubmed/) was used to search for citations from MEDLINE in the November 2009 time frame that con...

The purpose of this study was to examine risk factors for mortality in patients with type 1 diabetes. Baseline risk factors were measured in the EURODIAB Prospective Cohort Study with 2,787 type 1 diabetic patients (51% men and 49% women) recruited from 16 European countries. Mortality data were collected during a 7-year follow-up. There was an ann...

We assessed the effect upon A1C of recruitment to a clinical trial in patients with diabetes who had been screened and interviewed to determine eligibility but whose therapy was otherwise unchanged. Eligible trials were selected from the global program of an insulin manufacturer. Included were studies in which patients were seen on a single screeni...

We previously reported that treatment of acne with 13-cis-retinoic acid causes insulin resistance and disturbances in lipid metabolism resembling those of the insulin-resistance syndrome. It is not known whether this is associated with alterations in the concentrations of serum adiponectin, an insulin-sensitising hormone secreted by adipocytes. Ele...

Little information is available on cholesterol absorption and synthesis in human type 1 diabetes. We studied these variables using serum cholesterol precursor sterol ratios to cholesterol as surrogate markers of cholesterol synthesis and those of cholestanol and plant sterols to reflect cholesterol absorption in seven type 1 diabetic subjects and i...

Streptozotocin-induced type 1 diabetes in experimental animals inhibits cholesterol synthesis and increases cholesterol absorption. In contrast to human type 2 diabetes, virtually no information is available on cholesterol synthesis and absorption in type 1 diabetes. We studied the variables of cholesterol metabolism in 27 patients with type 1 diab...

To evaluate the effect of maternal diabetes on the concentrations of free and bound leptin at birth and during postnatal adaptation. Total, bound, and free leptin concentrations and the percentage of free leptin were measured in cord plasma and plasma at 3 days of age of 13 term infants of mothers with gestational diabetes mellitus (GDM) and 13 ter...

13-cis-Retinoic acid (Roaccutan) treatment is associated with disturbances in lipid and sometimes also in glucose metabolism. Thus, we investigated whether 13-cis-retinoic acid treatment decreases insulin sensitivity. We studied 11 men [aged 24+/-2 years (mean+/-SEM), body mass index (BMI) 22.1+/-0.9 kg/m(2)] who received Roaccutan treatment for ac...

Sulfonylureas stimulate insulin secretion independent of the blood glucose concentration. This can lead to hypoglycaemia in type 2 diabetic patients. Over the last years a number of imidazoline derivatives have been identified that stimulate insulin secretion in a more glucose-dependent way. In agreement with this, our aim was to generate imidazoli...

We studied the effect of an oral fat load on plasma acylation stimulating protein (ASP) concentrations in 9 lean healthy (age 59+/-2 years, body mass index [BMI] 23.2+/-0.4 kg/m(2); both mean+/-SEM), 9 obese nondiabetic (58+/-2 years, BMI 29.4+/-0.5 kg/m(2)), and 12 type 2 diabetic (60+/-2 years, BMI 29.6+/-1.0 kg/m(2)) men. Because ASP is a cleava...

We investigated the effect of carbohydrate availability and euglycaemic hyperinsulinaemia on intramuscular and plasma amino acids in 14 healthy men (age 26.5 +/- 0.9 years, b.m.i. 22.9 +/- 0.5 kg/m2). Insulin was infused (1.5 mU/kg/min) for 240 min both after a carbohydrate depleting exercise and after carbohydrate loading. Muscle samples were take...

Type 2 diabetes is characterized by increased acute phase serum proteins. We wanted to study how these proteins are related to complement activation in type 2 diabetes and how improvement of glycemic control affects them or complement activation. A total of 29 type 2 diabetic patients (age, 55.2 +/- 1.8 years, glycosylated hemoglobin [HbA(1c)] 8.9%...

Fatty acid transporter protein (FATP)-1 mRNA expression was investigated in skeletal muscle and in subcutaneous abdominal adipose tissue of 17 healthy lean, 13 nondiabetic obese, and 16 obese type 2 diabetic subjects. In muscle, FATP-1 mRNA levels were higher in lean women than in lean men (2.2 +/- 0.1 vs. 0.6 +/- 0.2 amol/microg total RNA, P < 0.0...

Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been suggested to be a part of the insulin resistance syndrome, and recent data suggest that adipose tissue participates in the production of PAI-1. We examined the expression and insulin regulation of subcutaneous adipose tissue PAI-1 mRNA and its relationship to insulin sen...

The purpose of this study was to examine whether fetal leptin concentration correlates with severity of chronic or subchronic fetal hypoxia as indicated by increased fetal concentrations of erythropoietin in fetuses of mothers with Type I (insulin dependent) diabetes mellitus. We measured leptin and erythropoietin concentrations in cord plasma and...

To study the effect of maternal pre-eclampsia on cord plasma leptin concentrations in preterm infants. Leptin concentration was analysed in cord plasma of 74 preterm infants, gestational age 24 to 32 weeks. Of these, 14 were born to pre-eclamptic mothers, in 10 intrauterine growth retardation (IUGR) was present, and 59 had been exposed antenatally...

Because estrogens stimulate the synthesis and release of leptin in the adipocytes, the effect of antiestrogens on the circulating leptin levels were studied. Thirty postmenopausal patients with breast cancer were randomized to start either with tamoxifen (20 mg/day, n=15) or toremifene (40 mg/day, n=15), and the patients were examined and serum lep...

An association with subcutaneous adipose tissue TNFalpha expression and insulin resistance has been suggested in obesity/type-2 diabetes, but this has not been examined directly. In the first part of the study we investigated whether this association is present in 7 lean, 10 obese nondiabetic and 9 type-2 diabetic men. In the second part of the stu...

Hyperleptinemia may be part of the insulin resistance syndrome. We studied serum leptin in preeclampsia, which is an insulin-resistant state, and sought associations between leptin and insulin or insulin sensitivity during and after pregnancy. Twenty-two proteinuric preeclamptic women and 16 normotensive controls were studied during the third trime...

Background. Complement protein C3 is vital to all three complement activation pathways. Chronic activation of the complement system may also have detrimental effects such as increased risk for cardiovascular disease. Previous literature suggest an association between serum C3 levels and the insulin resistance syndrome, but this has never been inves...

Inflammation could play a part in insulin resistance. Thiazolidinediones, new antidiabetic drugs, possess anti-inflammatory effects in vitro. We investigated if acute-phase serum proteins are increased in patients with Type II (non-insulin-dependent) diabetes mellitus who had been treated with insulin and whether troglitazone has anti-inflammatory...

1. The role of blood flow as a determinant of skeletal muscle glucose uptake is at present controversial and results of previous studies are confounded by possible direct effects of vasoactive agents on glucose uptake. Since increase in muscle blood flow can be due to increased flow velocity or recruitment of new capillaries, or both, it would be i...

To evaluate the quality of diabetes care at a national level in Finland, using level of glycemia as a determinant of success in treatment. Physicians and diabetes nurses in 76 randomly selected clinics (59 primary care units and 17 hospitals) evenly covering the whole of Finland were asked to fill in a questionnaire asking for data based on the 199...

Insulin Mix25 is a new premixed insulin analog containing 25% insulin lispro and 75% neutral protamine lispro (NPL) suspension (NPL insulin). The aim of the study was to compare serum glucose and insulin responses after breakfast in type 2 diabetic patients who received Mix25, premixed regular/NPH (30%/70%), or NPH insulin before the meal. We studi...

There are substantial alterations in fuel homeostasis immediately after birth. Leptin is a putative regulator of energy metabolism. Consequently, the aim of this study was to examine whether there are changes in circulating leptin concentrations during the early postnatal period. Umbilical cord mixed blood samples were taken at delivery, and a veno...

There are changes in the ability to regulate energy balance and caloric intake with aging. Consequently, we investigated whether human aging modifies the levels of serum leptin, a novel hormone implicated in the regulation of energy balance. We studied 268 Caucasian men and women aged 22-85 years, and divided them into groups with mean ages of 30,...

Leptin is an adipocyte-derived hormone that is thought to provide a negative feedback signal to control body fat mass by interacting with its hypothalamic receptor. The present study was undertaken to examine the uptake of leptin in cerebrospinal fluid (CSF) space in humans and whether the transport of leptin into CSF space is an active phenomenon...

The glucose transport proteins (GLUT1 and GLUT4) facilitate glucose transport into insulin-sensitive cells. GLUT1 is insulin-independent and is widely distributed in different tissues. GLUT4 is insulin-dependent and is responsible for the majority of glucose transport into muscle and adipose cells in anabolic conditions. We suggest the hypothesis t...

A precise time-action profile of insulin lispro (Humalog) at mealtime may reduce the incidence of severe hypoglycemia. Because it is a rare complication, we performed a cumulative meta-analysis to compare the frequency of severe hypoglycemia during insulin lispro and human regular insulin therapy in type 1 diabetic patients. The analysis included e...

Insulin-like growth factor binding protein-3 carries most of the circulating IGFs. While insulin regulates serum IGFBP-1 concentration, the effect of insulin on IGFBP-3 concentration is not known. We examined the IGFBP-3 response to hyperinsulinemia in healthy subjects and diabetic patients. Serum IGFBP-3 and IGF-I concentrations were measured duri...

To study the effect of lisinopril on the exercise-induced urinary albumin excretion rate. A total of 26 IDDM patients with normoalbuminuria were randomized into two groups, with one group receiving placebo (n = 13, age 36 +/- 3 years, BMI 24.5 +/- 1.1 kg/m2) and the other group receiving an average of 15 mg lisinopril daily (n = 13, age 34 +/- 2 ye...

Insulin lispro is a newly developed analogue of human insulin where the positions of the amino acids lysine and proline have been switched at the end of the B chain of the insulin molecule. Insulin lispro with lysine at position B28 and proline at position B29 has a weaker tendency for self-association than human insulin. This leads to three major...

To the Editor: The meta-analysis of Fath-Ordoubadi and Beatt1 suggests a beneficial role for glucose-insulin-potassium therapy for treatment of acute myocardial infarction in nondiabetic patients, a result in accordance with the recently reported beneficial effect in diabetic patients.2 Although the exact mechanisms behind the improvement of pr...

Leptin is a recently discovered hormone that appears as a regulator of energy balance. It is important to know whether leptin concentrations are changed under conditions of altered energy homeostasis. Consequently, we examined the effects of exercise with fasting and exercise with feeding on circulating leptin concentrations in healthy men and in t...

Leptin is a peptide hormone produced by adipocytes which provides a negative feedback signal to control the amount of body fat. The action of leptin on food intake and weight loss is thought to be mediated by interaction with its hypothalamic receptor. We examined the biodistribution and brain uptake of radioiodinated leptin (123I-leptin) by dynami...

Leptin is a peptide hormone produced by adipocytes which provides a negative feedback signal to control the amount of body fat. The action of leptin on food intake and weight loss is thought to be mediated by interaction with its hypothalamic receptor. We examined the biodistribution and brain uptake of radioiodinated leptin (123I-leptin) by dynami...

We have recently demonstrated in an uncontrolled study that glycemic control can be improved, when type 1 diabetic patients are transferred to insulin lispro and basal insulin regimen is optimized. We examined whether the better control can be maintained if the patients are transferred back to regular human insulin regimen. Eighty-four type 1 patie...

Unlabelled: Increased lipid oxidation is related to insulin resistance. Some of the enhanced lipid utilization may be derived from intramuscular sources. We studied muscle triglyceride (mTG) concentration and its relationship to insulin sensitivity in 10 healthy men (age 29 +/- 2 years, BMI 23.3 +/- 0.6 kg/m2) and 17 men with insulin-dependent dia...

The role of physical activity in the prevention of non-insulin-dependent diabetes mellitus (NIDDM) is of utmost importance. The aim of the present study was to evaluate the metabolic effects of aerobic endurance exercise and circuit-type resistance training in subjects with impaired glucose tolerance (IGT). Twenty-two individuals participated in th...

We examined whether hyperinsulinemia is associated with changes in the amount of L-carnitine and acetyl-L-carnitine in the muscle and whether the source of acetyl-coenzyme A (CoA) (glucose or free fatty acids [FFAs]) influences its further metabolism to acetyl-L-carnitine or through tricarboxylic acid in the skeletal muscle of man in vivo. Twelve h...

Leptin is an adipocyte-derived peptide hormone regulating energy balance in experimental animals. Although the physiological function of leptin in humans is still unclear, its secretion is closely related to fat mass in adult humans. To examine how fetal growth correlates with leptin levels at birth, an umbilical cord venous blood sample was obtain...

To examine whether overall glycemic control can be improved with insulin lispro by adjustment of the basal insulin regimen without an increased risk of hypoglycemia. A 5-month open study was performed in 66 IDDM patients after they had been transferred from human regular insulin to insulin lispro as a premeal therapy. The premeal and basal insulin...

Unlabelled: We studied the interrelationship between blood flow, glycogen synthesis, and glucose and lipid utilization in 14 healthy men. A 4-h euglycemic insulin clamp with indirect calorimetry and muscle biopsies were done after a glycogen depletion (exercise) and after a resting day (control). In spite of the exercise induced decrease in leg mu...

Owing to advances in the diagnosis and treatment of diabetic nephropathy, its management has become more active and is now initiated earlier after the presence of microalbuminuria has been established. In 1996 the Finnish Diabetic Association's nephropathy group issued recommendations concerning screening for diabetic nephropathy, and treatment and...

Insulin lispro is an insulin analog that was recently developed particularly for a mealtime therapy. It has a fast absorption rate and short duration of action. The efficacy of insulin lispro in the clinical therapy of patients with non-insulin-dependent diabetes mellitus (NIDDM) has not been tested. To compare insulin lispro and human regular insu...

We examined changes in serum leptin concentrations and thermogenesis in 12 healthy men (39 +/- 2 years, BMI 22.8 +/- 0.3 kg m-2) during a 4 h euglycaemic hyperinsulinaemia performed on a control day and after a day of competitive marathon runs. As compared with the control day, after the marathon, baseline FFA concentration (543 +/- 0.73 vs. 955 +/...

Sugar alcohols are used in food products, yet their metabolic effects in humans are poorly known. We examined plasma glucose, insulin, and C-peptide responses and changes in carbohydrate and lipid oxidation after the ingestion of 25 g lactitol, xylitol, or glucose. Eight healthy, nonobese men were studied after an overnight fast. After the ingestio...

Unlabelled: Acute physical exercise usually enhances insulin sensitivity. We examined the effect of a competitive 42 km marathon run on glucose uptake and lipid oxidation in 7 runners with insulin-dependent diabetes mellitus (IDDM), aged 36 +/- 3 yr, BMI 23.9 +/- 0.5 kg m-2, VO2max 46 +/- 1 ml kg-1 min-1, HbA1c 7.7 +/- 0.3%, duration of diabetes 1...

We studied the interrelationship between the obese gene product serum leptin, insulin and counter-regulatory hormone concentrations and glycogen synthesis in 26 healthy men. A 4-h euglycaemic insulin clamp with muscle biopsies was performed after a resting control day in 26 subjects, and in 14 of them also after heavy, glycogen-depleting (32%, P <...

Leptin, the product of the ob gene, reduces body fat in genetically obese animals and circulates in elevated concentrations in the blood of obese patients. Polymorphic markers situated in the proximity of the human ob gene have recently been suggested to be linked to morbid obesity. We have studied the possible association between the microsatellit...

The purpose of the study was to examine the prevalence and interrelationships of micro- and macrovascular complications and their risk factors in insulin-dependent (type 1) diabetic patients. The prevalence of nephropathy, retinopathy and cardiovascular disease was examined and their associations to risk factors (glycemic control, blood pressure, b...

Insulin stimulates ob gene expression and increases serum leptin concentrations in mice and in noninsulin-dependent diabetes mellitus patients. Obese women have higher ob gene messenger ribonucleic acid levels than obese men, suggesting that sex hormones are involved in the regulation of leptin synthesis. We studied the relationship among leptin, i...

The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms. The insulin analogue insulin lispro has a weak self-association and a fast absorption rate. We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus...

Insulin lispro, an insulin analog recently developed particularly for mealtime therapy, has a fast absorption rate and a short duration of action. We compared insulin lispro and regular human insulin in the mealtime treatment of 1,008 patients with IDDM. The study was a 6-month randomized multinational (17 countries) and multicenter (102 investigat...

Exercise is known to decrease insulin secretion, but the effect on insulin clearance is unclear. We examined the effect of exercise in insulin clearance with euglycaemic insulin clamp in 28 healthy men either 12 h after a marathon run (n = 14) or 44 h after a 2-h treadmill exercise (n = 14), and in seven insulin-dependent diabetes mellitus (IDDM) p...

Plasma levels of leptin, the recently discovered satiety hormone, are associated with adiposity in humans. To determine whether genetic factors or body fat distribution affect the association between leptin levels and obesity. 23 healthy identical twin pairs (9 male pairs and 14 female pairs, 33 to 59 years of age) who were discordant for obesity (...

The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms. The insulin analogue insulin lispro has a weak self-association and a fast absorption rate. We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus...

To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM C...

The aim of the present study was to examine both the structure, including modes of drug treatment, ambulatory care, and hospital inpatient care, and the costs of health care for drug-treated diabetic patients in Finland. The modes of drug treatment and ambulatory care were studied with the help of a questionnaire given to all diabetic patients obta...

To examine the acute effects of intravenous metoprolol and enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity. Randomized, single-blind, placebo-controlled trial. Helsinki University Central Hospital, Finland Seven moderately insulin-resistant nondiabetic subjects. Each subjects was studied three times at 2-3 week...

The aim of the study was to investigate the influence of outpatient care, overall hospital bed provision and the prevalence of diabetes on the hospital use by adult diabetic patients. Population based data were collected in Finland from a 3-year period. Hospital admissions, inpatient days, and mean length of stay due to diabetes were derived from t...

To examine the mechanisms by which immunosuppression by steroids impairs glycogen synthesis in human skeletal muscle, we measured glycogen synthase protein content and activity in muscle samples from 14 patients receiving corticosteroid therapy after kidney transplantation and in 20 healthy control subjects. A percutaneous muscle sample was taken b...

Acute physical exercise enhances insulin sensitivity in healthy subjects. We examined the effect of a 42-km marathon run on insulin sensitivity and lipid oxidation in 19 male runners. In the morning after the marathon run, basal serum free fatty acid concentration was 2.2-fold higher, muscle glycogen content 37% lower (P < 0.01), glycogen synthase...

Previous studies have suggested a reduced glucose uptake by the athlete's heart at rest. To examine whether there is a compensatory increase in the myocardial fatty acid utilization, we studied nine male endurance-trained athletes (age 26 ± 2 yr, ˙VO2max 60 ± 1 ml·kg-1·min-1, mean ± SEM) and eight sedentary subjects (age 26 ± 1 yr, ˙VO2max 38 ± 2 m...

In healthy men, both high and low serum testosterone concentrations are associated with insulin resistance, whereas low concentration of sex hormone binding globulin (SHBG) is related to reduced insulin sensitivity. The aim of our study was to examine the association of sex hormones, SHBG, dehydroepiandrosterone (DHEAS) and insulin-like growth fact...

OBJECTIVE In healthy men, both high and low serum testosterone concentrations are associated with insulin resistance, whereas low concentration of sex hormone binding globulin (SHBG) is related to reduced insulin sensitivity. The aim of our study was to examine the association of sex hormones, SHBG, dehydroeplandrosterone (DHEAS) and insulin-like g...

Essential hypertension is characterized by skeletal muscle insulin resistance but it is unknown whether insulin resistance also affects heart glucose uptake. We quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake rates in 10 mild essential hyp...

The acute effects of hyperinsulinemia on androgen homeostasis and a possible association of androgens to insulin sensitivity, serum lipids and lipoproteins and to lipid oxidation were examined in 19 healthy males (27 +/- 1 yrs, body mass index 24 +/- 1 kg/m2). In each subject, a 240 min euglycemic hyperinsulinemic clamp was performed and glucose an...

Physical exercise is traditionally recommended to diabetic patients as part of their treatment. Although healthy athletes exhibit enhanced skeletal muscle insulin sensitivity, the metabolic effects of vigorous training in patients with insulin-dependent diabetes mellitus (IDDM) are not known. This study was designed to examine the effects of compet...