| 96301. |
- Lundqvist, Lena, et al.
(författare)
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Profiling and activity screening of Dammarane-type triterpen saponins from Gynostemma pentaphyllum with glucose-dependent insulin secretory activity
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The global prevalence of type 2 diabetes is increasing rapidly; consequently there is great need for new and novel therapeutic options. Gynostemma pentaphyllum (GP) is a traditional medicinal plant, mainly present in Southeast Asian countries, that has been reported to exert antidiabetic effects, by stimulating insulin secretion. The specific compound responsible for this effect is however as yet unidentified. Screening for discovery and identification of bioactive compounds of an herbal GP extract, was performed in isolated pancreatic islets from spontaneously diabetic Goto-Kakizaki (GK) rats, a model of type 2 diabetes, and from non-diabetic control Wistar rats. From this herbal extract 27 dammarane-type saponins, including two novel compounds, were isolated and their structure was elucidated by mass spectrometry and NMR spectroscopy. One of the dammarane-type triterpenoid showed a glucose-dependent insulin secretion activity. This compound, gylongiposide I, displays unique abilities to stimulate insulin release at high glucose levels (16.7 mM), but limited effects at a low glucose concentration (3.3 mM). Further studies on this compound, also in vivo, are warranted with the aim of developing a novel anti-diabetic therapeutic with glucose-dependent insulinogenic effect.
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| 96302. |
- Lundqvist, Martina, et al.
(författare)
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Cost-Effectiveness of the Use of Gold Anchor (TM) Markers in Prostate Cancer
- 2020
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Ingår i: Cureus. - : CUREUS INC. - 2168-8184. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A common treatment for prostate cancer is external beam radiation therapy. A way to target the radiation is to use implantable gold fiducial markers (GFMs). The GFMs serve as reference points enabling tumor localization during treatment. Today, there are several GFMs available on the market but no clinical guidelines as to which one to use. The aim of this study was to estimate the cost-effectiveness of Gold Anchor GFMs (Naslund Medical AB, Huddinge, Sweden) implanted with a 22G needle, compared to other GFMs implanted with a 17-18G needle, in the prostate gland of patients with prostate cancer. Methods Costs, life years, and quality-adjusted life years (QALYs) were estimated over a lifelong time horizon for each treatment strategy using a decision-analytic model. Data used in the model were obtained from published literature or were estimated by an expert elicitation technique. The primary outcome measure was an incremental cost-effectiveness ratio (ICER). Results Gold Anchor GFM was found to be a dominant alternative with both lower costs [-8.7 US Dollars (USD)] and a gain in QALYs (0.015) when compared with other GFMs. The lower cost was achieved by fewer visits for imaging in treatment planning, and by reduced risk of infections and sepsis. The QALY gain was driven by a reduced risk of sepsis. Conclusion The use of Gold Anchor GFMs as reference points to target radiation is a cost-effective alternative when compared to other GFMs. However, this analysis is based on expert elicitation regarding some crucial parameters, and further clinical studies of the use of GFMs are needed.
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| 96303. |
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| 96304. |
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| 96305. |
- Lundqvist, Martin H., et al.
(författare)
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Altered hormonal and autonomic nerve responses to hypo- and hyperglycaemia are found in overweight and insulin-resistant individuals and may contribute to the development of type 2 diabetes
- 2021
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 64:3, s. 641-655
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Results from animal models and some clinical work suggest a role for the central nervous system (CNS) in glucose regulation and type 2 diabetes pathogenesis by modulation of glucoregulatory hormones and the autonomic nervous system (ANS). The aim of this study was to characterise the neuroendocrine response to various glucose concentrations in overweight and insulin-resistant individuals compared with lean individuals.Methods: Overweight/obese (HI, n = 15, BMI ≥27.0 kg/m2) and lean (LO, n = 15, BMI <27.0 kg/m2) individuals without diabetes underwent hyperinsulinaemic euglycaemic–hypoglycaemic clamps and hyperglycaemic clamps on two separate occasions with measurements of hormones, Edinburgh Hypoglycaemic Symptom Scale (ESS) score and heart rate variability (HRV). Statistical methods included groupwise comparisons with Mann–Whitney U tests, multilinear regressions and linear mixed models between neuroendocrine responses and continuous metabolic variables.Results: During hypoglycaemic clamps, there was an elevated cortisol response in HI vs LO (median ΔAUC 12,383 vs 4793 nmol/l × min; p = 0.050) and a significantly elevated adrenocorticotropic hormone (ACTH) response in HI vs LO (median ΔAUC 437.3 vs 162.0 nmol/l × min; p = 0.021). When adjusting for clamp glucose levels, obesity (p = 0.033) and insulin resistance (p = 0.009) were associated with elevated glucagon levels. By contrast, parasympathetic activity was less suppressed in overweight individuals at the last stage of hypoglycaemia compared with euglycaemia (high-frequency power of HRV, p = 0.024). M value was the strongest predictor for the ACTH and PHF responses, independent of BMI and other variables. There was a BMI-independent association between the cortisol response and ESS score response (p = 0.024). During hyperglycaemic clamps, overweight individuals displayed less suppression of glucagon levels (median ΔAUC −63.4% vs −73.0%; p = 0.010) and more suppression of sympathetic relative to parasympathetic activity (low-frequency/high-frequency power, p = 0.011).Conclusions/interpretation: This study supports the hypothesis that altered responses of insulin-antagonistic hormones and the ANS to glucose fluctuations occur in overweight and insulin-resistant individuals, and that these responses are probably partly mediated by the CNS. Their potential role in development of type 2 diabetes needs to be addressed in future research.
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| 96306. |
- Lundqvist, M. H., et al.
(författare)
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Augmented cortisol-axis and symptom response to hypoglycaemia in individuals with overweight and insulin resistance
- 2020
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:SUPPL 1, s. S236-S236
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: An important role of the CNS in the pathogenesis of type 2 diabetes (T2D) has been suggested and is supported by animal studies. The brain senses fluctuations in systemic glucose levels and modulates glucoregulatory hormones and autonomic nerve activity to balance glucose levels. We hypothesize that the brain’s setpoint for glucose is gradually shifted upwards in the development of T2D. The aim of this study was to investigate if the neuroendocrine response to varying glucose levels differ in overweight and insulin-resistant compared to control subjects.Materials and methods: 30 subjects with no diagnosis of diabetes were recruited and allocated into two groups based on the median BMI: LO [BMI 23.4 kg/m2 (Range 18.9-26.9)] and HI [BMI 32.0 (27.0-48.7) kg/ m2 ]. Age and gender distribution were similar. On two separate occasions and in a randomized order, stepwise hypoglycemic (nadir 2.7 mM) and hyperglycemic (max +9 mM) clamps were performed with repeated measurements of hormones (glucagon, cortisol, ACTH, growth hormone), assessment of symptoms according to the Edinburgh Hypoglycemia Symptom Scale (ESS) and monitoring of heart rate variability (HRV). Mann-Whitney U-tests were used for group-wise comparisons.Results: In HI vs LO the response to hypoglycemia was augmented for both cortisol [ΔAUC 12382 nM*min (IQR 7058;15705) vs 4792(- 1200;11498, p=0.045] and ACTH [ΔAUC 448.3 pM*min (373.5;702.0) vs 162.0 (125.3;397.5), p=0.015]. Subjects in HI reported higher peak ESS Scores [21 (19;23) vs 18 (14;21), p=0.045] during hypoglycemia. By contrast, subjects in HI had loss of suppression of PHF (an HRV marker of parasympathetic nerve activity) during hypoglycemia [0.035 ms2 log (- 0.353;0.188) vs -0.219 ms2 log (-0.476;-0.132), p= 0.024]. The above perturbations were independently associated with insulin resistance but not with obesity per se according to multilinear regressions (Table). During hyperglycemia there was a trend toward higher glucagon levels in HI vs LO [AUC 539.5 pM*min (336.9;617.2) vs 390.5 pM*min (244.5;476.2), p=0.085). Subjects in HI had lower mean PLF/ PHF ratio, a marker of balance between sympathetic and parasympathetic nerve activity [0.383 (0.260;0.568) vs 0.154 (0.081;0.299), p=0.005].Conclusion: Overweight, insulin-resistant subjects had more symptoms during hypoglycemia and this was combined with central cortisol axis overactivity via pituitary ACTH release, altogether suggesting altered CNS responses. They also had less dynamic autonomic nerve activity. These neuroendocrine alterations were associated with insulin resistance independent of obesity, supporting a role of the brain in raising the glycemic setpoint in the development of T2D.
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| 96307. |
- Lundqvist, Martin H., et al.
(författare)
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Health care registers can be instrumental for endpoint capture in clinical diabetes trials : example of microvascular complications in Swedish patients with type 2 diabetes
- 2023
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Ingår i: Diabetes & Vascular Disease Research. - : Sage Publications. - 1479-1641 .- 1752-8984. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: SMARTEST is a register-based randomized clinical trial (RRCT) that compares dapagliflozin to metformin in early-stage type 2 diabetes. The primary outcome includes progression of microvascular complications based on data from the Swedish National Diabetes Register (NDR). In this sub-study, the aim was to validate microvascular complication variables in the NDR against electronic health records (EHRs).METHODS: Data were extracted from EHRs of 276 SMARTEST participants with a median observation period of 3 years in the Uppsala, Örebro and Sörmland counties and compared with NDR data. Agreement was determined for all corresponding data entries as well as for progression of microvascular complications after randomization.RESULTS: The agreement for all corresponding data entries was 98.9% (Intraclass Correlation Coefficient 0.999) for creatinine and eGFR, 95.1% for albuminuria, 91.6% for foot-at-risk and 98.2% for retinopathy status (Kappa 0.67-0.91). The agreement for progression of microvascular complications was 98.0% for CKD stage, 98.9% for albuminuria grade, 96.3% for foot-at-risk grade and 99.6% for retinopathy grade progression (Gwet's AC1 0.96-1.00). CONCLUSION: Microvascular complication variables in the NDR show good agreement with EHR data. The use of a well-established national health care registry, exemplified by the NDR, for endpoint collection in RRCTs such as SMARTEST is supported by this study.
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| 96308. |
- Lundqvist, Martin H., et al.
(författare)
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Regulation of the Cortisol Axis, Glucagon, and Growth Hormone by Glucose Is Altered in Prediabetes and Type 2 Diabetes
- 2024
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 109:2, s. e675-e688
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Tidskriftsartikel (refereegranskat)abstract
- Context Insulin-antagonistic, counter-regulatory hormones have been implicated in the development of type 2 diabetes (T2D).Objective In this cross-sectional study, we investigated whether glucose-dependent regulation of such hormones differ in individuals with T2D, prediabetes (PD), and normoglycemia (NG).Methods Fifty-four individuals with or without T2D underwent one hyperinsulinemic-normoglycemic-hypoglycemic and one hyperglycemic clamp with repeated hormonal measurements. Participants with T2D (n = 19) were compared with a group-matched (age, sex, BMI) subset of participants without diabetes (ND, n = 17), and also with participants with PD (n = 18) and NG (n = 17).Results In T2D vs ND, glucagon levels were higher and less suppressed during the hyperglycemic clamp whereas growth hormone (GH) levels were lower during hypoglycemia (P < .05). Augmented ACTH response to hypoglycemia was present in PD vs NG (P < .05), with no further elevation in T2D. In contrast, glucagon and GH alterations were more marked in T2D vs PD (P < .05). In the full cohort (n = 54), augmented responses of glucagon, cortisol, and ACTH and attenuated responses of GH correlated with adiposity, dysglycemia, and insulin resistance. In multilinear regressions, insulin resistance was the strongest predictor of elevated hypoglycemic responses of glucagon, cortisol, and ACTH. Conversely, fasting glucose and HbA1c were the strongest predictors of low GH levels during hypoglycemia and elevated, i.e. less suppressed glucagon levels during hyperglycemia, respectively. Notably, adiposity measures were also strongly associated with the responses above.Conclusions Altered counter-regulatory hormonal responses to glucose variations are observed at different stages of T2D development and may contribute to its progression by promoting insulin resistance and dysglycemia.
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| 96309. |
- Lundqvist, Martin
(författare)
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Insulin-antagonistic neurohormonal pathways in the development of insulin resistance and type 2 diabetes
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- According to the current paradigm, the development of type 2 diabetes is driven by insulin resistance and the gradual failure of beta cells to compensate for this by secreting adequate amounts of insulin. Obesity is an important risk factor for type 2 diabetes and is considered to influence disease development primarily by induction of insulin resistance, via mechanisms that have not been fully elucidated. Insulin-antagonistic, counter-regulatory neurohormonal pathways, including glucagon, cortisol (stimulated by the pituitary hormone ACTH), growth hormone and the autonomic nervous system have glucose-raising properties and constitute a physiological defense to hypoglycemia that is coordinated from the brain and brainstem. Glucose variations also trigger responses of several inflammatory mediators, that may also oppose the actions of insulin. The overarching aim of this thesis was to explore the importance of glucose-dependent dysregulation of these counter-regulatory pathways – hormonal, neural and inflammatory – in the development of type 2 diabetes. All selected papers in this thesis are based on data obtained during stepwise hyperinsulinemic-euglycemic-hypoglycemic clamps and hyperglycemic clamps, in which glucose levels are lowered or raised to prespecified target levels. In papers I and II, we found that overweight and insulin resistance was associated with cortisol/ACTH hyperreactivity to hypoglycemia and general hyperglucagonemia, insensitive to glucose-dependent suppression. Furthermore, in paper I, the autonomic nervous system was more rigid to glucose variations in overweight and insulin resistant individuals, with a failure to inhibit parasympathetic activity during hypoglycemia and an attenuated activity of sympathetic relative to parasympathetic activity during hyperglycemia. In paper III, cortisol/ACTH hyperreactivity was present already in individuals with prediabetes, with no further exacerbation in individuals with type 2 diabetes. By contrast, hyperglycemia-insensitive hyperglucagonemia and, in addition, general growth hormone downregulation was found to be more pronounced in individuals with type 2 diabetes. In paper IV, no unfavorably altered reactivity of inflammatory markers was found in obese compared to lean individuals. In conclusion, glucose-dependent dysregulation of several insulin-antagonistic neurohormonal pathways appears to be present at different stages of type 2 diabetes development and may drive disease development via aggravation of insulin resistance.
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| 96310. |
- Lundqvist, Peter
(författare)
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Jaboulay gastroduodenostomy for pyloric obstruction after corrosive ingestion
- 2020
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Ingår i: Journal of Pediatric Surgery Case Reports. - : Elsevier BV. - 2213-5766. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Strong acid accidental ingestion is a common case in rural society and children. The effect of strong acids may cause injuries of the gastrointestinal tract. We present a case obstruction in the distal part of gastric after accidental sulfuric acid ingestion in children. Sulfuric acid ingestion is potential in children since its commercial product physical appearance looks like drink water. Then the patient was diagnosed with pyloric obstruction after barium meal examination and was treated using Jaboulay gastroduodenostomy procedure.
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