Squatting test: A posture to study and counteract cardiovascular abnormalities associated with autonomic dysfunction.

The squatting test is an active posture manoeuvre that imposes one of the most potent orthostatic stresses. In normal subjects, the changes in blood pressure and heart rate are transient because of appropriate baroreflex homeostasis and do not provoke symptoms. However, in various pathological conditions, both the increase in blood pressure during squatting and the decrease in blood pressure during standing may be more important and sustained, potentially leading to complaints and adverse events. Squatting has been used to evaluate patients with tetralogy of Fallot, heart transplant, dysautonomia, including diabetic cardiovascular autonomic neuropathy, and individuals prone to vasovagal syncope. Careful analysis of changes in blood pressure and heart rate during the transition from standing to squatting and from squatting to standing allows the early detection of altered vagal and/or sympathetic function. Of note squatting position has been proposed as a therapeutic means to counteract the fall in blood pressure in patients suffering from dizziness due to dysautonomia and orthostatic hypotension or presenting pre-syncope symptoms, such as soon after exercise. The aims of the present review are to analyse the haemodynamic pattern during a squatting test in various pathological situations and to describe what may be the negative and positive haemodynamic changes associated with this posture. We were especially interested in using the squatting test for the assessment of cardiovascular autonomic neuropathy associated with diabetes mellitus

Dizziness: hypoglycemia, hypotension or spasmophilia?

peer reviewedThe consultation for dizziness is a common problem in clinical practice. Because of the apparent lack of specificity of the complaints, there is a rather high risk to prescribe a variety of sophisticated exams, which will not be very helpful in absence of a well oriented anamnesis and a pertinent clinical examination. The present paper aims at describing a global medical approach, essentially based upon a detailed anamnesis (semiological, chronological and therapeutical arguments), to which may be added a few simple clinical and technical complementary data. This strategy should allow obtaining quite easily pertinent arguments for a differential diagnosis between reactive hypoglycaemia, (orthostatic) hypotension, and hyperventilation crisis (spasmophilia)

Glycemic Risk Index (GRI) variability in type 1 diabetes adults with HbA1c ≤ 7%: insights for clinical evaluation and intervention

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Pulse pressure and cardiovascular autonomic neuropathy according to duration of type 1 diabetes.

peer reviewedBACKGROUND: To evaluate changes in pulse pressure (PP) and markers of cardiovascular autonomic neuropathy (CAN) according to duration of type 1 diabetes mellitus (T1DM). METHODS: This cross-sectional controlled study evaluated 159 diabetic patients during a 3-min posture test (standing-squatting-standing) with continuous measurement of systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure by a Finapres device. Arterial stiffness was indirectly assessed by PP and the slope of PP as a function of MBP calculated during the whole 3-min test. CAN was assessed by the expiration/inspiration pulse interval ratio (E/I R-R ratio) during deep breathing and by three indices measured during the squatting test. Patients were divided into four groups according to diabetes duration ( 30 years from group 1 to group 4, respectively) and compared with age-matched non-diabetic subjects. RESULTS: PP progressively increased (p < 0.0001) and PP/MBP decreased (p < 0.0005) according to T1DM duration, whereas these parameters remained almost unchanged in age-matched control subjects. E/I ratio (p < 0.0001) and baroreflex gain (p < 0.0005) progressively decreased with T1DM duration. The parasympathetic index (squatting test vagal ratio-SqTv) significantly increased (p < 0.0001), whereas the sympathetic index (squatting test sympathetic ratio-SqTs) only tended to decrease (p = 0.12) according to diabetes duration. No such changes in CAN indices were observed in the non-diabetic population. CONCLUSIONS: PP increased according to T1DM duration in an age range where PP remained almost stable in controls, in agreement with accelerated arterial stiffening due to chronic hyperglycaemia. The baroreflex gain decreased and other indices of CAN also deteriorated with diabetes duration, more so indices reflecting parasympathetic rather than sympathetic dysfunction

CONTRIBUTION TO THE STUDY OF CARDIOVASCULAR AUTONOMIC NEUROPATHY AND PULSATILE STRESS IN PATIENTS WITH TYPE 1 DIABETES

Le diabète de type 1 (DT1) atteint des sujets jeunes, impose une prise en charge astreignante au quotidien et expose les personnes avec un contrôle glycémique insuffisant à un risque de complications chroniques parfois graves. Notre travail s’est intéressé à deux complications fréquentes, mais moins bien connues, du DT1, la neuropathie autonome cardiovasculaire (NAC), d’une part, la rigidité artérielle, d’autre part. Nous avons étudié ces deux anomalies en mesurant de façon continue et non invasive les variations de la pression artérielle (PA) et de la fréquence cardiaque (FC) à l’aide d’un Finapres® lors d’un test postural original, le test dit de « squatting ». En analysant les variations instantanées de PA et de FC lors du passage de la position debout à la position accroupie puis lors de la transition de la position accroupie à la position debout, nous avons démontré que le patient DT1 est exposé à une augmentation de la pression différentielle (pression pulsée ou PP) et à un stress pulsatile accru (témoin indirect d’une rigidité artérielle précoce) et à une diminution de la sensibilité du baro-réflexe (témoin d’une dysfonction autonome touchant d’abord le versant parasympathique puis sympathique).Nous avons analysé de façon systématique, dans des études transversales et longitudinales, une série de facteurs susceptibles d’influencer la survenue et la progression de ces complications et nous avons tenté de corréler les anomalies objectivées en ce qui concerne la NAC et le stress pulsatile avec d’autres complications comme la présence d’une microalbuminurie.Cette thèse a été divisée en deux grandes parties, la première consacrée à la NAC et au gain baro-réflexe (GBR), la seconde consacrée au stress pulsatile et à la rigidité artérielle.1)NAC et GBRLes principaux résultats de cette partie du travail peuvent être résumés succinctement de la façon suivante : 1) la mesure du GBR lors d’un test de squatting est suffisamment reproductible pour être exploitée dans des investigations cliniques ; 2) une diminution progressive du GBR est observée dans la population DT1 avec la durée d’évolution du diabète (données transversales), plus rapide que la diminution attribuée à l’âge si l’on compare à une population témoin non diabétique appariée ; 3) cette altération du GBR est apparemment plus marquée chez les femmes DT1 que chez les hommes DT1, pour une raison qui n’apparaît pas clairement ; 4) la diminution du GBR mise en évidence dans une étude longitudinale de quelques années est plus prononcée chez les patients DT1 mal équilibrés (HbA1c > 8 %) que chez ceux bien équilibrés ; enfin, 5) le GBR s’avère plus performant que les indices basés sur les seules variations de la FC comme les indices SqTv et SqTs mesurés lors d’un test de squatting ou encore l’indice classique R-R E/I ratio calculé lors d’une respiration à 6 cycles par minutes, pour discriminer les sujets DT1 avec d’autres complications, comme une augmentation du stress pulsatile ou encore une microalbuminurie, marqueur d’une néphropathie débutante.2)Stress pulsatile et rigidité artérielleLes principaux résultats de cette partie du travail peuvent être résumés comme suit :1) la mesure de PP et du stress pulsatile lors d’un test de squatting est remarquablement reproductible permettant son exploitation dans des investigations cliniques ; 2) une augmentation (par ailleurs accentuée en position accroupie) progressive de PP et du stress pulsatile est observée dans la population DT1 avec la durée d’évolution du diabète (données transversales), plus rapide que l’accroissement lié simplement à l’âge si l’on compare à une population témoin non diabétique appariée ; 3) cette élévation de PP est sensiblement plus marquée chez les femmes DT1 que chez les hommes DT1, ce qui pourrait contribuer à l’augmentation bien connue du risque de morbi-mortalité CV dans la population féminine diabétique ; 4) l’augmentation de PP et du stress pulsatile mise en évidence dans une étude longitudinale de quelques années est plus marquée chez les patients DT1 mal équilibrés (HbA1c > 8 %) que chez ceux bien équilibrés, en accord avec le rôle délétère de l’hyperglycémie chronique; 5) l’augmentation de PP et du stress pulsatile observée à la cinquantaine chez le patient DT1 (après une vingtaine d’années d’évolution de la maladie) est comparable à celle du patient DT2 avec une durée d’évolution connue de la maladie moins longue (5-6 années), mais avec d’autres facteurs de risque CV bien connus regroupés habituellement dans ce qu’il est convenu d’appeler le syndrome métabolique; enfin, 6) PP et le stress pulsatile sont corrélés avec d’autres marqueurs de risque chez le patient diabétique comme la NAC (attestée par un GBR diminué) et la microalbuminurie comme marqueur précoce de néphropathie débutante (et peut-être aussi de dysfonction endothéliale).Nous espérons, par ce travail avoir contribué à une meilleure connaissance de deux complications, sous-estimées et trop souvent méconnues, susceptibles de toucher les patients présentant un DT1 évoluant de longue date avec un équilibre glycémique insuffisant, la NAC et la rigidité artérielle.Cette thèse est sous-tendue par 6 articles de revue (dont 4 dans des journaux internationaux), par 6 articles originaux (publiés dans des revues scientifiques internationales et tous comme premier auteur) et par 6 résumes de congrès (non encore publiés comme articles complets, les nombreux autres résumés de congrès ayant abouti aux articles originaux n’étant pas comptabilisés ici). Ces divers documents peuvent être consultés dans les annexes à la fin de ce travail où le lecteur intéressé pourra aussi trouver des résumés et des informations complémentaires si nécessaire.CONTRIBUTION TO THE STUDY OF CARDIOVASCULAR AUTONOMIC NEUROPATHY AND PULSATILE STRESS IN PATIENTS WITH TYPE 1 DIABETESJean-Christophe PHILIPSSUMMARYType 1 diabetes mellitus (T1DM) mostly affects young people. Intensive daily treatment and global management of the disease are generally difficult to achieve and these patients, when poor metabolic control is chronically present, may be exposed to severe complications as diabetes duration increases. Our work aims to study two frequent but underestimated diabetic complications : cardiovascular autonomic neuropathy (CAN) and pulsatile stress, as an indirect marker arterial stiffness. The deleterious effects of both CAN and arterial stiffness, especially their role in increasing cardiovascular and total mortality in T1DM patients, are discussed in the introduction. In addition, the most important methods used in the literature to assess the presence of CAN and arterial stiffness are described in order to put our personal contribution in perspective. In the present experimental work, changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured continuously with a Finapres® device during an original standardized orthostatic test called the “squatting test” (1 minute standing – 1 minute squatting – 1 minute standing). As discussed in the first part of our work, previous experimental studies have validated the use of the Finapres® device for non-invasive monitoring of arterial BP (similar results as with direct arterial BP measurements), including when rapid changes occur as during specific manoeuvres used to test cardiovascular reflexes. When analyzing beat-to-beat variations of BP and HR during the two transition phases of the squatting test (stand-to-squat and squat-to-stand), we demonstrated that T1DM patients show higher pulse pressure (PP = SBP minus DSP) and higher pulsatile stress (PP x HR, in order to take into account the potential influence of HR – which may be influence by CAN- on PP), especially in the squatting position. Both increased PP and pulsatile stress are considered as indirect markers of arterial stiffness. In addition, we used the changes in SBP and HR occurring during the squat-stand transition in order to calculate a so-called baroreflex gain by plotting the pulse intervals (R-R) against systolic BP levels, the slope of the relation reflecting baroreflex sensitivity as previously shown by using classical pharmacological tests. Descreased baroreflex gain is related to CAN and global autonomic dysfunction, affecting the parasympathetic nervous system first, then the sympathetic system, in the natural history of diabetic neuropathy. We showed that T1DM patients have a decreased baroreflex sensitivity, which may be detected in the squat-stand test in an early stage of the disease, even when other CAN indices are still within the normal range.We systematically collected different data related to factors possibly involved in the presence and the progression of these two diabetic complications in transversal and longitudinal studies. We also tested possible relationships between CAN, pulsatile stress and other diabetic complications, microalbuminuria in particular.This work is divided in two major parts: the first one studying CAN and the baroreflex gain, the second one being dedicated to the pulsatile stress and arterial stiffness.CAN and baroreflex gainMajor findings in this part of the work can be summarized as follows:-Squatting test is a valuable manoeuvre to assess the baroreflex gain, and the reproducibility of the measurement is good enough to propose this approach in clinical studies.-Baroreflex gain significantly decreases with diabetes duration in T1DM patients in an age range where such a reduction does not reach statistical significance in a matched non-diabetic population. -The baroreflex gain decreases with diabetes duration more in T1DM women compared to men, for an unknown reason.-In a longitudinal study, baroreflex gain significantly decreases in T1DM patients with inadequate control of diabetes (HbA1c > 8%), but not in patients with a better glycaemic status (HbA1c ≤ 8%).-Evaluation of the baroreflex gain is a better tool to identify T1DM patients with other complications (presence of microalbuminuria or higher pulsatile stress) than simpler indices only derived from HR changes during a squatting test (SqTv and SqTs, two indices previously proposed to assess CAN during such a posture manoeuvre) and the classic R-R interval Expiratory/Inspiratory ratio (R-R E/I ratio) calculated during the deep-breathing test.Pulsatile stress and arterial stiffness Main results of this part of the work are:-Measurements of PP and pulsatile stress using the Finapres® device during a standardized squatting test are very reproducible and can be used in clinical investigations.-Transversal studies show an increase of PP and pulsatile stress (particularly in the squatting position) as diabetes duration increases. Such an increase is not seen in a matched non-diabetic population.-PP increases more in T1DM women than in T1DM men; this observation may partially explain why diabetic women are particularly exposed to cardiovascular disease.-Patients with worst diabetic control (HbA1c > 8%) show greater increases in PP and pulsatile stress than T1DM patients with a better control (HbA1c ≤ 8%), confirming the pejorative role of hyperglycaemia in the cardiovascular status of diabetic patients.-Middle-aged (mean 50 years old) T1DM patients with a diabetes duration of more than 20 years have a similar increase of PP and pulsatile stress as age-matched type 2 diabetic patients with a shorter disease duration (5 to 6 years) but exposed to the metabolic syndrome (hypertension excluded), another well-known cardiovascular risk factor.-In T1DM patients, PP and the pulsatile stress are well correlated to other cardiovascular risk factors like CAN (confirmed by a decreased baroreflex gain) and the presence of microalbuminuria (an early marker of diabetic nephropathy and possibly endothelial dysfunction).DISCUSSION AND CONCLUSIONThe general discussion of the present work is divided into four sections : 1) a critical analysis (discussing both advantages and limits) of the original standardized posture test used in our laboratory, the so-called squatting test, combined with a continuous monitoring of BP and HR with the Finapres® device; 2) a synthesis of our own contribution in the study of CAN, by emphasizing the potential interest of assessing the baroreflex gain and comparing our original observations with the most important data of the literature;3) a synthesis of our personal contribution in the study of arterial stiffness, by assessing indirect markers such as PP and pulsatile stress, and again by comparing our results with most relevant ones from the literature; 4) finally, an integrative view of the global (cardiovascular and renal) risk to which poorly controlled T1DM patients are exposed in the long term and in which both CAN and arterial stiffness obviously play an aggravating role. Hopefully, this work may contribute to a better understanding of two underestimated but frequent diabetic complications, CAN and arterial stiffness. T1DM patients with longer disease duration and an inadequate metabolic control are at higher risk for these complications, both closely related to the global cardiovascular and renal risk.Recent experimental data collected in our laboratory and summarized in this work have been discussed in 4 review articles (3 published in international peer-reviewed journals), presented in 6 original papers (all published as first author in international journals) and summarized in 8 congress abstracts (numerous other abstracts including different data or corresponding to data finally published in full papers have not been taken in account). Major publications supporting this work are printed at the end of the document

Effets de la durée du diabète de type 1 sur la pression artérielle pulsée : résultats d’une étude transversale comparative à un groupe contrôle non diabétique.

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Contribution of continuous glucose measurement in the management of gestational diabetes: A pilot study

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Arterial pulse pressure in relation to the duration of type 1 diabetes: a cross-sectional controlled study

Diabetes mellitus and arterial pulse pressure (PP) are two independent cardiovascular risk factors. This cross-sectional study investigated the influence of diabetes duration on PP in type 1 diabetic patients without any cardiovascular disease. PP was measured continuously during 3 minutes (active orthostatic test: 1 min standing--1 min squatting--1 min standing) using a fingertip plethysmograph (Finapres) in 159 type 1 diabetic patients aged 20-60 yrs. They were divided into 4 groups according to diabetes duration: (1) G1 : 30 yrs (n=18). In order to separate the effects of age from the effects of diabetes duration, diabetic patients were compared to age- and sex-matched non diabetic controls. PP (expressed in mmHg; mean +/- SD) was higher in men than in women in both diabetic (58 +/- 15 vs. 50 +/- 14; p = 0.001) and non diabetic subjects (55 +/- 14 vs. 47 +/- 12; p = 0.001). Overall PP was higher in diabetic than in non diabetic individuals (54 +/- 15 vs. 50 +/- 13; p = 0.025). PP progressively increased according to diabetes duration: 47 +/- 16 vs. 51 +/- 13 vs. 59 +/- 14 vs. 62 +/- 12, from G1 to G4 respectively; p or =8% (55 +/- 16), with (57 +/- 17) or without (54 +/- 14) microalbuminuria, treated (56 +/- 14) or not (54 +/- 15) by inhibitors of the renin-angiotensin system. In conclusion, PP progressively increased with the duration of type 1 diabetes, independently of age. Such increase was more marked in squatting than in standing position. The role of such PP rise in the increased cardiovascular risk of patients with type 1 diabetes, although suspected in the recent EURODIAB Prospective Complications Study, deserves further investigation

Les inhibiteurs de SGLT2. L’EXPÉRIENCE BELGE

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